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Open AccessEditorial

Translational Aspects of Cardiovascular Biology: From Bench to Bedside

by Gaetano Santulli

Biology 2023, 12(5), 658; https://doi.org/10.3390/biology12050658 - 27 Apr 2023

Viewed by 1458

Abstract

Cardiovascular disease is the leading cause of death worldwide, and the search for novel mechanisms and therapeutics is desperately needed [...] Full article

(This article belongs to the Special Issue Translational Aspects of Cardiovascular Biology: From Bench to Bedside)

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Research

Jump to: Editorial, Review

10 pages, 2566 KiB

Open AccessCommunication

miR-4432 Targets FGFBP1 in Human Endothelial Cells

by Roberta Avvisato, Pasquale Mone, Stanislovas S. Jankauskas, Fahimeh Varzideh, Urna Kansakar, Jessica Gambardella, Antonio De Luca, Alessandro Matarese and Gaetano Santulli

Biology 2023, 12(3), 459; https://doi.org/10.3390/biology12030459 - 16 Mar 2023

Cited by 5 | Viewed by 2583

Abstract

MicroRNAs (miRs) are small non-coding RNAs that modulate the expression of several target genes. Fibroblast growth factor binding protein 1 (FGFBP1) has been associated with endothelial dysfunction at the level of the blood–brain barrier (BBB). However, the underlying mechanisms are mostly unknown and [...] Read more.

MicroRNAs (miRs) are small non-coding RNAs that modulate the expression of several target genes. Fibroblast growth factor binding protein 1 (FGFBP1) has been associated with endothelial dysfunction at the level of the blood–brain barrier (BBB). However, the underlying mechanisms are mostly unknown and there are no studies investigating the relationship between miRs and FGFBP1. Thus, the overarching aim of the present study was to identify and validate which miR can specifically target FGFBP1 in human brain microvascular endothelial cells, which represent the best in vitro model of the BBB. We were able to identify and validate miR-4432 as a fundamental modulator of FGFBP1 and we demonstrated that miR-4432 significantly reduces mitochondrial oxidative stress, a well-established pathophysiological hallmark of hypertension. Full article

(This article belongs to the Special Issue Translational Aspects of Cardiovascular Biology: From Bench to Bedside)

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15 pages, 1768 KiB

Open AccessArticle

Tissue and Serum Biomarkers in Degenerative Aortic Stenosis-Insights into Pathogenesis, Prevention and Therapy

by Alkistis Kapelouzou, Styliani Geronikolou, Irene Lidoriki, Christos Kontogiannis, Loukas Kaklamanis, Loukas Tsourelis and Dennis V. Cokkinos

Biology 2023, 12(3), 347; https://doi.org/10.3390/biology12030347 - 22 Feb 2023

Cited by 4 | Viewed by 2244

Abstract

Background and Aim. Degenerative Aortic Stenosis (DAS) is a common disease that causes substantial morbidity and mortality worldwide, especially in the older population. Our aim was to further investigate novel serum and tissue biomarkers to elucidate biological processes involved in this entity. Material [...] Read more.

Background and Aim. Degenerative Aortic Stenosis (DAS) is a common disease that causes substantial morbidity and mortality worldwide, especially in the older population. Our aim was to further investigate novel serum and tissue biomarkers to elucidate biological processes involved in this entity. Material and Methods. We evaluated the expression of six biomarkers significantly involved in cardiovascular pathology, i.e., irisin, periostin, osteoglycin, interleukin 18, high mobility group box 1 and proprotein convertase subtilisin/kexin type 9 in the serum at the protein level, and in the tissue at both the protein and mRNA levels of patients with AS (N = 60). Five normal valves obtained after transplantation from hearts of patients with idiopathic dilated cardiomyopathy were also studied. Serum measurements were also performed in 22 individuals without valvular disease who served as controls (C). Results. Higher levels of all factors were found in DAS patients’ serum than in normal C. IHC and PCR mRNA tissue analysis showed the presence of all biomarkers in the aortic valve cusps with DAS, but no trace of PCR mRNA was found in the five transplantation valves. Moreover, periostin serum levels correlated significantly with IHC and mRNA tissue levels in AS patients. Conclusion. We showed that six widely prevalent biomarkers affecting the atherosclerotic process were also involved in DAS, suggesting a strong osteogenic and pro-inflammatory profile, indicating that aortic valve calcification is a multifactorial biological process. Full article

(This article belongs to the Special Issue Translational Aspects of Cardiovascular Biology: From Bench to Bedside)

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22 pages, 5574 KiB

Open AccessArticle

Anticancer Drugs Paclitaxel, Carboplatin, Doxorubicin, and Cyclophosphamide Alter the Biophysical Characteristics of Red Blood Cells, In Vitro

by Elisaveta Skverchinskaya, Nadezhda Levdarovich, Alexander Ivanov, Igor Mindukshev and Anton Bukatin

Biology 2023, 12(2), 230; https://doi.org/10.3390/biology12020230 - 31 Jan 2023

Cited by 6 | Viewed by 3108

Abstract

Red blood cells (RBCs) are the most numerous cells in the body and perform gas exchange between all tissues. During the infusion of cancer chemotherapeutic (CT) agents, blood cells are the first ones to encounter aggressive cytostatics. Erythrocyte dysfunction caused by direct cytotoxic [...] Read more.

Red blood cells (RBCs) are the most numerous cells in the body and perform gas exchange between all tissues. During the infusion of cancer chemotherapeutic (CT) agents, blood cells are the first ones to encounter aggressive cytostatics. Erythrocyte dysfunction caused by direct cytotoxic damage might be a part of the problem of chemotherapy-induced anemia—one of the most frequent side effects. The aim of the current study is to evaluate the functional status of RBCs exposed to mono and combinations of widely used commercial pharmaceutical CT drugs with different action mechanisms: paclitaxel, carboplatin, cyclophosphamide, and doxorubicin, in vitro. Using laser diffraction, flow cytometry, and confocal microscopy, we show that paclitaxel, having a directed effect on cytoskeleton proteins, by itself and in combination with carboplatin, caused the most marked abnormalities—loss of control of volume regulation, resistance to osmotic load, and stomatocytosis. Direct simulations of RBCs’ microcirculation in microfluidic channels showed both the appearance of a subpopulation of cells with impaired velocity (slow damaged cells) and an increased number of cases of occlusions. In contrast to paclitaxel, such drugs as carboplatin, cyclophosphamide, and doxorubicin, whose main target in cancer cells is DNA, showed significantly less cytotoxicity to erythrocytes in short-term exposure. However, the combination of drugs had an additive effect. While the obtained results should be confirmed in in vivo models, one can envisioned that such data could be used for minimizing anemia side effects during cancer chemotherapy. Full article

(This article belongs to the Special Issue Translational Aspects of Cardiovascular Biology: From Bench to Bedside)

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14 pages, 3250 KiB

Open AccessArticle

Identification and Verification of Biomarkers and Immune Infiltration in Obesity-Related Atrial Fibrillation

by Zhonghui Xie, Chuanbin Liu, Xu Lu, Zhijie Chen, Nan Zhang, Xinyan Wang, Xiaoqian Li and Yang Li

Biology 2023, 12(1), 121; https://doi.org/10.3390/biology12010121 - 12 Jan 2023

Cited by 5 | Viewed by 2361

Abstract

Obesity is an independent risk factor for atrial fibrillation (AF). However, the mechanisms underlying this crosstalk are still being uncovered. Co-differentially expressed genes (co-DEGs) of AF and obesity microarrays were identified by bioinformatics analysis. Subsequently, functional enrichment, cell-type enrichment, and protein–protein interaction network [...] Read more.

Obesity is an independent risk factor for atrial fibrillation (AF). However, the mechanisms underlying this crosstalk are still being uncovered. Co-differentially expressed genes (co-DEGs) of AF and obesity microarrays were identified by bioinformatics analysis. Subsequently, functional enrichment, cell-type enrichment, and protein–protein interaction network analyses of co-DEGs were carried out. Then, we validated the hub genes by qRT-PCR of patients’ blood samples. Finally, CIBERSORT was utilized to evaluate the AF microarray to determine immune infiltration and the correlation between validated hub genes and immune cells. A total of 23 co-up-regulated DEGs in AF and obesity microarrays were identified, and these genes were enriched in inflammation- and immune-related function. The enriched cells were whole blood, CD33+ myeloid, and CD14+ monocytes. The hub genes were identified as MNDA, CYBB, CD86, FCGR2C, NCF2, LCP2, TLR8, HLA-DRA, LCP1, and PTPN22. All hub genes were only elevated in blood samples of obese-AF patients. The CIBERSORT analysis revealed that the AF patients’ left atrial appendage had increased infiltration of naïve B cells and decreased infiltration of memory B cells. The hub genes were related positively to naïve B cells and negatively to memory B cells. Ten hub genes may serve as biomarkers for obesity-related AF. These findings may also aid in comprehending pathophysiological mechanisms for obesity-related AF. Full article

(This article belongs to the Special Issue Translational Aspects of Cardiovascular Biology: From Bench to Bedside)

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17 pages, 23964 KiB

Open AccessArticle

IDH1 Promotes Foam Cell Formation by Aggravating Macrophage Ferroptosis

by Ben Li, Chufan Wang, Peng Lu, Yumeng Ji, Xufeng Wang, Chaoyang Liu, Xiaohu Lu, Xiaohan Xu and Xiaowei Wang

Biology 2022, 11(10), 1392; https://doi.org/10.3390/biology11101392 - 23 Sep 2022

Cited by 21 | Viewed by 3431

Abstract

A distinctive feature of ferroptosis is intracellular iron accumulation and the impairment of antioxidant capacity, resulting in a lethal accumulation of lipid peroxides leading to cell death. This study was conducted to determine whether inhibiting isocitrate dehydrogenase 1 (IDH1) may help to prevent [...] Read more.

A distinctive feature of ferroptosis is intracellular iron accumulation and the impairment of antioxidant capacity, resulting in a lethal accumulation of lipid peroxides leading to cell death. This study was conducted to determine whether inhibiting isocitrate dehydrogenase 1 (IDH1) may help to prevent foam cell formation by reducing oxidized low-density lipoprotein (ox-LDL)-induced ferroptosis in macrophages and activating nuclear factor erythroid 2-related factor 2 (NRF2). Gene expression profiling (GSE70126 and GSE70619) revealed 21 significantly different genes, and subsequent bioinformatics research revealed that ferroptosis and IDH1 play essential roles in foam cell production. We also confirmed that ox-LDL elevates macrophage ferroptosis and IDH1 protein levels considerably as compared with controls. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, reduced ox-LDL-induced elevated Fe²⁺ levels, lipid peroxidation (LPO) buildup, lactate dehydrogenase (LDH) buildup, glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4), ferritin heavy polypeptide 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11) protein downregulation. More crucially, inhibiting IDH1 reduced Fe²⁺ overload, lipid peroxidation, LDH, and glutathione depletion, and elevated GPX4, FTH1, and SLC7A11 protein expression, resulting in a reduction in ox-LDL-induced macrophage ferroptosis. IDH1 inhibition suppressed ox-LDL-induced macrophage damage and apoptosis while raising NRF2 protein levels. We have demonstrated that inhibiting IDH1 reduces ox-LDL-induced ferroptosis and foam cell formation in macrophages, implying that IDH1 may be an important molecule regulating foam cell formation and may be a promising molecular target for the treatment of atherosclerosis. Full article

(This article belongs to the Special Issue Translational Aspects of Cardiovascular Biology: From Bench to Bedside)

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12 pages, 1124 KiB

Open AccessArticle

Trophism and Homeostasis of Liver Sinusoidal Endothelial Graft Cells during Preservation, with and without Hypothermic Oxygenated Perfusion

by Francesco Vasuri, Giuliana Germinario, Carmen Ciavarella, Michele Carroli, Ilenia Motta, Sabrina Valente, Matteo Cescon, Antonia D’Errico, Gianandrea Pasquinelli and Matteo Ravaioli

Biology 2022, 11(9), 1329; https://doi.org/10.3390/biology11091329 - 8 Sep 2022

Cited by 4 | Viewed by 1916

Abstract

The aim of the present study was to evaluate the homeostasis and trophism of liver sinusoidal endothelial cells (LSECs) in vivo in different stages of liver graft donation, in order to understand the effects of graft ischemia and perfusion on LSEC activity in [...] Read more.

The aim of the present study was to evaluate the homeostasis and trophism of liver sinusoidal endothelial cells (LSECs) in vivo in different stages of liver graft donation, in order to understand the effects of graft ischemia and perfusion on LSEC activity in liver grafts. Special attention was paid to grafts that underwent hypothermic oxygenated perfusion (HOPE). Forty-seven donors were prospectively enrolled, and two distinct biopsies were performed in each case: one allocation biopsy (at the stage of organ allocation) and one post-perfusion biopsy, performed after graft implant in the recipients. In all biopsies, immunohistochemistry and RT-PCR analyses were carried out for the endothelial markers CD34, ERG, Nestin, and VEGFR-2. We observed an increase in CD34 immunoreactivity in LSEC during the whole preservation/perfusion period (p < 0.001). Nestin and ERG expression was low in allocation biopsies, but increased in post-perfusion biopsies, in both immunohistochemistry and RT-PCR (p < 0.001). An inverse correlation was observed between ERG positivity and donor age. Our results indicate that LSEC trophism is severely depressed in liver grafts, but it is restored after reperfusion in standard conditions. The execution of HOPE seems to improve this recovery, confirming the effectiveness of this machine perfusion technique in restoring endothelial functions. Full article

(This article belongs to the Special Issue Translational Aspects of Cardiovascular Biology: From Bench to Bedside)

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12 pages, 644 KiB

Open AccessArticle

Correlation between Carbonic Anhydrase Isozymes and the Evolution of Myocardial Infarction in Diabetic Patients

by Sorina Magheru, Calin Magheru, Florin Maghiar, Liliana Sachelarie, Felicia Marc, Corina Maria Moldovan, Laura Romila, Anica Hoza, Dorina Maria Farcas, Irina Gradinaru and Loredana Liliana Hurjui

Biology 2022, 11(8), 1189; https://doi.org/10.3390/biology11081189 - 8 Aug 2022

Cited by 1 | Viewed by 1944

Abstract

(1) Background: Myocardial infarction was, until recently, recognized as a major coronary event, often fatal, with major implications for survivors. According to some authors, diabetes mellitus is an important atherogenic risk factor with cardiac determinations underlying the definition of the so-called “diabetic heart”. [...] Read more.

(1) Background: Myocardial infarction was, until recently, recognized as a major coronary event, often fatal, with major implications for survivors. According to some authors, diabetes mellitus is an important atherogenic risk factor with cardiac determinations underlying the definition of the so-called “diabetic heart”. The present study aims to establish a correlation between the evolution of myocardial infarction in diabetic patients, by determining whether lactic acid levels, the activity of carbonic anhydrase isoenzymes, and the magnitude of ST-segment elevation are correlated with the subsequent evolution of myocardial infarction. (2) Methods: The study analyzed 2 groups of 30 patients each: group 1 consisted of diabetic patients with acute myocardial infarction, and group 2 consisted of non-diabetic patients with acute myocardial infarction. Patients were examined clinically and paraclinical, their heart markers, lactic acid, and the activity of carbonic anhydrase I and II isozymes were determined. All patients underwent electrocardiogram and echocardiography analyses. (3) Results: The results showed that diabetics develop acute myocardial infarction more frequently, regardless of how much time has passed since the diagnosis. The value of myocardial necrosis enzymes was higher in diabetics than in non-diabetics, and acute coronary syndrome occurs mainly in diabetics with poor metabolic balance. Lethality rates in non-diabetic patients with lactic acid values above normal are lower than in diabetics. (4) Conclusions: Lactic acid correlated with the activity of isozyme I of carbonic dioxide which could be early markers of the prognosis and evolution of diabetic patients with acute myocardial infarction. Full article

(This article belongs to the Special Issue Translational Aspects of Cardiovascular Biology: From Bench to Bedside)

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11 pages, 4204 KiB

Open AccessArticle

Recovery of Ischemic Limb and Femoral Artery Endothelial Function Are Preserved in Mice with Dextran Sodium Sulfate-Induced Chronic Colitis

by Hao Wu, Qiang Zhu, Xuanyou Liu, Hong Hao, Zhe Sun, Meifang Wang, Michael A. Hill, Canxia Xu and Zhenguo Liu

Biology 2022, 11(8), 1169; https://doi.org/10.3390/biology11081169 - 4 Aug 2022

Cited by 2 | Viewed by 2095

Abstract

Inflammatory bowel disease (IBD) produces significant systemic inflammation and increases the risk of endothelial dysfunction and peripheral artery disease. Our recent study demonstrated that abdominal aortic endothelial cell function was impaired selectively in female mice with chronic colitis. This study aimed to test [...] Read more.

Inflammatory bowel disease (IBD) produces significant systemic inflammation and increases the risk of endothelial dysfunction and peripheral artery disease. Our recent study demonstrated that abdominal aortic endothelial cell function was impaired selectively in female mice with chronic colitis. This study aimed to test the hypothesis that experimental colitis leads to femoral artery endothelial cell dysfunction and impairs limb ischemia recovery in female mice. An experimental chronic colitis model was created in female C57BL/6 mice with dextran sodium sulfate (DSS) treatment. Unilateral hind limb ischemia was produced by femoral artery ligation. Limb blood perfusion, vascular density, tissue ROS levels, and plasma levels of proinflammatory cytokines were assessed. Femoral artery endothelium-dependent and -independent vasodilation of the contralateral limb were evaluated ex vivo using acetylcholine and nitroglycerin, respectively. As expected, the plasma levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-17, were significantly increased in the DSS-induced colitis model. However, ROS levels in the ischemic muscle tissues were not significantly increased in colitis model as compared to the controls. There were no significant changes in endothelium-dependent or -independent vasodilation of the femoral artery between colitis model and the control. Recovery of function and blood flow in the ischemic limb and capillary density in the ischemic gastrocnemius muscle were preserved in the colitis model as compared with the control. The data demonstrated that DSS-induced chronic colitis had no significant impact on femoral artery endothelial function or ischemic limb recovery in female mice. Full article

(This article belongs to the Special Issue Translational Aspects of Cardiovascular Biology: From Bench to Bedside)

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21 pages, 3315 KiB

Open AccessArticle

Neuregulin (NRG-1β) Is Pro-Myogenic and Anti-Cachectic in Respiratory Muscles of Post-Myocardial Infarcted Swine

by Cristi L. Galindo, Van Thuan Nguyen, Braxton Hill, Ethan Easterday, John H. Cleator and Douglas B. Sawyer

Biology 2022, 11(5), 682; https://doi.org/10.3390/biology11050682 - 29 Apr 2022

Cited by 3 | Viewed by 3131

Abstract

Neuregulin-1β (NRG-1β) is a growth and differentiation factor with pleiotropic systemic effects. Because NRG-1β has therapeutic potential for heart failure and has known growth effects in skeletal muscle, we hypothesized that it might affect heart failure-associated cachexia, a severe co-morbidity characterized by a [...] Read more.

Neuregulin-1β (NRG-1β) is a growth and differentiation factor with pleiotropic systemic effects. Because NRG-1β has therapeutic potential for heart failure and has known growth effects in skeletal muscle, we hypothesized that it might affect heart failure-associated cachexia, a severe co-morbidity characterized by a loss of muscle mass. We therefore assessed NRG-1β’s effect on intercostal skeletal muscle gene expression in a swine model of heart failure using recombinant glial growth factor 2 (USAN-cimaglermin alfa), a version of NRG-1β that has been tested in humans with systolic heart failure. Animals received one of two intravenous doses (0.67 or 2 mg/kg) of NRG-1β bi-weekly for 4 weeks, beginning one week after infarct. Based on paired-end RNA sequencing, NRG-1β treatment altered the intercostal muscle gene expression of 581 transcripts, including genes required for myofiber growth, maintenance and survival, such as MYH3, MYHC, MYL6B, KY and HES1. Importantly, NRG-1β altered the directionality of at least 85 genes associated with cachexia, including myostatin, which negatively regulates myoblast differentiation by down-regulating MyoD expression. Consistent with this, MyoD was increased in NRG-1β-treated animals. In vitro experiments with myoblast cell lines confirmed that NRG-1β induces ERBB-dependent differentiation. These findings suggest a NRG-1β-mediated anti-atrophic, anti-cachexia effect that may provide additional benefits to this potential therapy in heart failure. Full article

(This article belongs to the Special Issue Translational Aspects of Cardiovascular Biology: From Bench to Bedside)

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12 pages, 1825 KiB

Open AccessArticle

Differences in Extracellular NAD⁺ and NMN Metabolism on the Surface of Vascular Endothelial Cells

by Patrycja Jablonska, Paulina Mierzejewska, Marta Tomczyk, Patrycja Koszalka, Marika Franczak, Ada Kawecka, Barbara Kutryb-Zajac, Alicja Braczko, Ryszard T. Smolenski and Ewa M. Slominska

Biology 2022, 11(5), 675; https://doi.org/10.3390/biology11050675 - 27 Apr 2022

Cited by 3 | Viewed by 3558

Abstract

The disruption of the metabolism of extracellular NAD⁺ and NMN may affect related signaling cascades and pathologies, such as cardiovascular or respiratory system diseases. We aimed to study NAD⁺ and NMN hydrolysis on surface endothelial cells of diverse origins and with [...] Read more.

The disruption of the metabolism of extracellular NAD⁺ and NMN may affect related signaling cascades and pathologies, such as cardiovascular or respiratory system diseases. We aimed to study NAD⁺ and NMN hydrolysis on surface endothelial cells of diverse origins and with genetically modified nucleotide catabolism pathways. We tested lung endothelial cells isolated from C57BL/6 J wild-type (WT) and C57BL/6 J CD73 knockout (CD73 KO) mice, the transfected porcine iliac artery endothelial cell line (PIEC) with the human E5NT gene for CD73 (PIEC CD73), and a mock-transfected control (PIEC MOCK), as well as HMEC-1 and H5V cells. Substrate conversion into the product was followed by high-performance liquid chromatography (HPLC). We showed profound differences in extracellular NAD⁺ and NMN metabolism related to the vessel origin, species diversity, and type of culture. We also confirmed the involvement of CD38 and CD73 in NAD⁺ and NMN cleavage. Full article

(This article belongs to the Special Issue Translational Aspects of Cardiovascular Biology: From Bench to Bedside)

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16 pages, 1329 KiB

Open AccessArticle

Retinol-Binding Protein-4—A Predictor of Insulin Resistance and the Severity of Coronary Artery Disease in Type 2 Diabetes Patients with Coronary Artery Disease

by Sangeetha Perumalsamy, Wan Azman Wan Ahmad and Hasniza Zaman Huri

Biology 2021, 10(9), 858; https://doi.org/10.3390/biology10090858 - 1 Sep 2021

Cited by 10 | Viewed by 2921

Abstract

(1) Background: Insulin resistance (IR) is the fundamental cause of type 2 diabetes (T2D), which leads to endothelial dysfunction and alters systemic lipid metabolism. The changes in the endothelium and lipid metabolism result in atherosclerotic coronary artery disease (CAD). In insulin-resistant and atherosclerotic [...] Read more.

(1) Background: Insulin resistance (IR) is the fundamental cause of type 2 diabetes (T2D), which leads to endothelial dysfunction and alters systemic lipid metabolism. The changes in the endothelium and lipid metabolism result in atherosclerotic coronary artery disease (CAD). In insulin-resistant and atherosclerotic CAD states, serum cytokine retinol-binding protein-4 (RBP-4) levels are elevated. The adipocyte-specific deletion of glucose transporter 4 (GLUT4) results in higher RBP-4 expression and IR and atherosclerotic CAD progression. (2) Aim: This study aimed to investigate the association of RBP-4 and clinical factors with IR and the severity of CAD. (3) Methods: Patients were recruited from diabetes and cardiology clinics and divided into three subgroups, namely (i) T2D patients with CAD, (ii) T2D-only patients, and (iii) CAD-only patients. The severity of CAD was classified as either single-vessel disease (SVD), double-vessel disease (DVD), or triple-vessel disease (TVD). An enzyme-linked immunosorbent assay was conducted to assess the concentration of serum RBP-4. Univariate (preliminary analysis) and multivariate (secondary analysis) logistic regressions were applied to assess the associations of RBP-4 and clinical factors with IR and the severity of CAD. (4) Results: Serum RBP-4 levels were associated with IR and the severity of CAD in all the three groups (all p-values are less than 0.05). Specifically, serum RBP-4 levels were associated with IR (p = 0.030) and the severity of CAD (SVD vs. DVD, p = 0.044; SVD vs. TVD, p = 0.036) in T2D patients with CAD. The clinical factors fasting plasma glucose (FPG) and angiotensin-converting-enzyme inhibitor (ACEI) were also associated with both IR and the severity of CAD in T2D patients with CAD. (5) Conclusion: RBP-4, FPG, and ACEI are predictors of IR and severity of CAD in T2D patients with CAD. Full article

(This article belongs to the Special Issue Translational Aspects of Cardiovascular Biology: From Bench to Bedside)

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10 pages, 1593 KiB

Open AccessEditor’s ChoiceArticle

The Effect of a 13-Valent Conjugate Pneumococcal Vaccine on Circulating Antibodies Against Oxidized LDL and Phosphorylcholine in Man, A Randomized Placebo-Controlled Clinical Trial

by Hendrika W. Grievink, Pim Gal, Maria Ozsvar Kozma, Erica S. Klaassen, Johan Kuiper, Jacobus Burggraaf, Christoph J. Binder and Matthijs Moerland

Biology 2020, 9(11), 345; https://doi.org/10.3390/biology9110345 - 22 Oct 2020

Cited by 7 | Viewed by 2804

Abstract

In mice vaccination with Streptococcus pneumoniae results in an increase in anti-oxLDL IgM antibodies due to mimicry of anti-phosphorylcholine (present in the cell wall of S. pneumoniae) and anti-oxLDL IgM. In this study we investigated the human translation of this molecular mimicry [...] Read more.

In mice vaccination with Streptococcus pneumoniae results in an increase in anti-oxLDL IgM antibodies due to mimicry of anti-phosphorylcholine (present in the cell wall of S. pneumoniae) and anti-oxLDL IgM. In this study we investigated the human translation of this molecular mimicry by vaccination against S. pneumoniae using the Prevenar-13 vaccine. Twenty-four healthy male volunteers were vaccinated with Prevenar-13, either three times, twice or once in a double-blind, placebo-controlled, randomized single center clinical study. Anti-pneumococcal wall, oxLDL and phosphorycholine antibody levels were measured at a fixed serum dilution, as well as circulating lipid levels over the course of 68 weeks. A significant increase in anti-oxLDL IgG and IgM was seen in the group receiving two doses six months apart compared to the placebo. However, these differences were not observed in the groups receiving a single dose, two doses one month apart, or three doses. This study shows that vaccination with Prevenar-13 does not result in robust anti-oxLDL IgM levels in humans. Further research would be required to test alternative pneumococcal-based vaccines, vaccination regimens or study populations, such as cardiovascular disease patients. Full article

(This article belongs to the Special Issue Translational Aspects of Cardiovascular Biology: From Bench to Bedside)

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15 pages, 1337 KiB

Open AccessReview

The Function and Therapeutic Potential of lncRNAs in Cardiac Fibrosis

by Xiang Nie, Jiahui Fan and Dao Wen Wang

Biology 2023, 12(2), 154; https://doi.org/10.3390/biology12020154 - 19 Jan 2023

Cited by 2 | Viewed by 2080

Abstract

Cardiac fibrosis remains an unresolved problem in cardiovascular diseases. Fibrosis of the myocardium plays a key role in the clinical outcomes of patients with heart injuries. Moderate fibrosis is favorable for cardiac structure maintaining and contractile force transmission, whereas adverse fibrosis generally progresses [...] Read more.

Cardiac fibrosis remains an unresolved problem in cardiovascular diseases. Fibrosis of the myocardium plays a key role in the clinical outcomes of patients with heart injuries. Moderate fibrosis is favorable for cardiac structure maintaining and contractile force transmission, whereas adverse fibrosis generally progresses to ventricular remodeling and cardiac systolic or diastolic dysfunction. The molecular mechanisms involved in these processes are multifactorial and complex. Several molecular mechanisms, such as TGF-β signaling pathway, extracellular matrix (ECM) synthesis and degradation, and non-coding RNAs, positively or negatively regulate myocardial fibrosis. Long noncoding RNAs (lncRNAs) have emerged as significant mediators in gene regulation in cardiovascular diseases. Recent studies have demonstrated that lncRNAs are crucial in genetic programming and gene expression during myocardial fibrosis. We summarize the function of lncRNAs in cardiac fibrosis and their contributions to miRNA expression, TGF-β signaling, and ECMs synthesis, with a particular attention on the exosome-derived lncRNAs in the regulation of adverse fibrosis as well as the mode of action of lncRNAs secreted into exosomes. We also discuss how the current knowledge on lncRNAs can be applied to develop novel therapeutic strategies to prevent or reverse cardiac fibrosis. Full article

(This article belongs to the Special Issue Translational Aspects of Cardiovascular Biology: From Bench to Bedside)

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32 pages, 2113 KiB

Open AccessReview

The Interplay of Hypoxia Signaling on Mitochondrial Dysfunction and Inflammation in Cardiovascular Diseases and Cancer: From Molecular Mechanisms to Therapeutic Approaches

by Esmaa Bouhamida, Giampaolo Morciano, Mariasole Perrone, Asrat E. Kahsay, Mario Della Sala, Mariusz R. Wieckowski, Francesco Fiorica, Paolo Pinton, Carlotta Giorgi and Simone Patergnani

Biology 2022, 11(2), 300; https://doi.org/10.3390/biology11020300 - 12 Feb 2022

Cited by 30 | Viewed by 6534

Abstract

Cardiovascular diseases (CVDs) and cancer continue to be the primary cause of mortality worldwide and their pathomechanisms are a complex and multifactorial process. Insufficient oxygen availability (hypoxia) plays critical roles in the pathogenesis of both CVDs and cancer diseases, and hypoxia-inducible factor 1 [...] Read more.

Cardiovascular diseases (CVDs) and cancer continue to be the primary cause of mortality worldwide and their pathomechanisms are a complex and multifactorial process. Insufficient oxygen availability (hypoxia) plays critical roles in the pathogenesis of both CVDs and cancer diseases, and hypoxia-inducible factor 1 (HIF-1), the main sensor of hypoxia, acts as a central regulator of multiple target genes in the human body. Accumulating evidence demonstrates that mitochondria are the major target of hypoxic injury, the most common source of reactive oxygen species during hypoxia and key elements for inflammation regulation during the development of both CVDs and cancer. Taken together, observations propose that hypoxia, mitochondrial abnormality, oxidative stress, inflammation in CVDs, and cancer are closely linked. Based upon these facts, this review aims to deeply discuss these intimate relationships and to summarize current significant findings corroborating the molecular mechanisms and potential therapies involved in hypoxia and mitochondrial dysfunction in CVDs and cancer. Full article

(This article belongs to the Special Issue Translational Aspects of Cardiovascular Biology: From Bench to Bedside)

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