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Effects of Dyslipidemia and Metabolic Syndrome on Cardiac and Vascular Dysfunction

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 March 2024) | Viewed by 25090

Special Issue Editors

Dr. Isotta Chimenti

E-Mail Website
Guest Editor
Department of Medical and Surgical Sciences and Biotechnology, Faculty of Pharmacy and Medicine, Sapienza University of Rome, 04100 Latina, Italy
Interests: cardiac microenvironment; cardiac repair mechanisms; 3D culture
Special Issues, Collections and Topics in MDPI journals
Dr. Vittoria Cammisotto

E-Mail Website
Co-Guest Editor
Department of Clinical Internal, Anaesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy
Interests: platelet activation; oxidative stress; inflammation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Dysmetabolic conditions, such as hyperglycemia, insulin resistance, dyslipidemia, metabolic syndrome and type 2 diabetes, affect an increasing number of people worldwide. They represent important risk factors for cardiovascular diseases, including cardiac remodeling and atherosclerosis, although many related pathogenetic mechanisms still require further elucidation. For example, lipids and lipid droplets accumulating in cardiomyocytes are common phenotypic features of dyslipidemia and metabolic syndrome in heart disease. Dyslipidemia in metabolic syndrome is characterized by rich apolipoprotein (apo) B-100 particles and high levels of triglycerides, and is an established risk factor for cardiovascular disease. Other features of dyslipidemia in metabolic syndrome are specific atherosclerotic phenotypes characterized by small, low-density lipoprotein cholesterol (LDL-C), low levels of high-density lipoprotein cholesterol (HDL-C) and altered platelet function. The role of dyslipidemia and metabolic syndrome in cardiac dysfunction involves a variety of pathological metabolic mechanisms, such as changes in oxidation and fatty acid uptake caused by impaired insulin signals and changes in the lipoprotein profile and lipoprotein receptor. These events lead to altered basic functions and signal pathways, such as fat oxidation and phagocytosis regulating autophagy, thus affecting the fate of cardiomyocytes and vascular cells and their resistance to stress. In addition, immune signal modulation, such as the pro-inflammatory or anti-inflammatory effects of lipid droplets, occurs under specific circumstances. The discovery of novel pathogenetic mechanisms in cardiac remodeling and dysfunction will pave the way for new exploitable therapeutic targets.

Dr. Isotta Chimenti
Dr. Vittoria Cammisotto
Guest Editors

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Keywords

  • lipid metabolism
  • glucose metabolism
  • oxidized lipids
  • cardiac fibrosis
  • cardiac remodeling
  • inflammatory signals
  • lipoprotein receptors
  • insulin resistance
  • autophagy
  • platelet activation
  • oxidative stress

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Published Papers (5 papers)

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Research

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19 pages, 3902 KiB  
Article
Therapeutic Aspects of Prunus cerasus Extract in a Rabbit Model of Atherosclerosis-Associated Diastolic Dysfunction
by Reka Szekeres, Daniel Priksz, Rita Kiss, Dana Diana Romanescu, Mariann Bombicz, Balazs Varga, Rudolf Gesztelyi, Anna Szilagyi, Barbara Takacs, Vera Tarjanyi, Beata Pelles-Tasko, Ildiko Forgacs, Judit Remenyik, Zoltan Szilvassy and Bela Juhasz
Int. J. Mol. Sci. 2023, 24(17), 13253; https://doi.org/10.3390/ijms241713253 - 26 Aug 2023
Viewed by 1453
Abstract
This study evaluates the potential therapeutic effects of anthocyanin-rich Prunus cerasus (sour cherry) extract (PCE) on atherosclerosis-associated cardiac dysfunction, described by the impairment of the NO-PKG (nitric oxide–protein kinase G) pathway and the antioxidant capacity. Initially, a rabbit model of atherosclerotic cardiovascular disease [...] Read more.
This study evaluates the potential therapeutic effects of anthocyanin-rich Prunus cerasus (sour cherry) extract (PCE) on atherosclerosis-associated cardiac dysfunction, described by the impairment of the NO-PKG (nitric oxide–protein kinase G) pathway and the antioxidant capacity. Initially, a rabbit model of atherosclerotic cardiovascular disease was established by administering a cholesterol-rich diet, enabling the examination of the impact of 9 g/kg PCE on the pre-existing compromised cardiovascular condition. After that, the animals were divided into four groups for 12 weeks: the (1) untreated control group; (2) PCE-administered healthy rabbits; (3) hypercholesterolemic (HC) group kept on an atherogenic diet; and (4) PCE-treated HC group. Dyslipidemia, impaired endothelial function, and signs of diastolic dysfunction were evident in hypercholesterolemic rabbits, accompanied by a reduced cardiac expression of eNOS (endothelial nitric oxide synthase), PKG, and SERCA2a (sarco/endoplasmic reticulum calcium ATPase 2a). Subsequent PCE treatment improved the lipid profile and the cardiac function. Additionally, PCE administration was associated with elevated myocardial levels of eNOS, PKG, and SERCA2a, while no significant changes in the vascular status were observed. Western blot analysis further revealed hypercholesterolemia-induced increase and PCE-associated reduction in heme oxygenase-1 expression. The observed effects of anthocyanins indicate their potential as a valuable addition to the treatment regimen for atherosclerosis-associated cardiac dysfunction. Full article
(This article belongs to the Special Issue Effects of Dyslipidemia and Metabolic Syndrome on Cardiac and Vascular Dysfunction)
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22 pages, 7237 KiB  
Article
Streptozotocin-Induced Type 1 and 2 Diabetes Mellitus Mouse Models Show Different Functional, Cellular and Molecular Patterns of Diabetic Cardiomyopathy
by Fabiola Marino, Nadia Salerno, Mariangela Scalise, Luca Salerno, Annalaura Torella, Claudia Molinaro, Antonio Chiefalo, Andrea Filardo, Chiara Siracusa, Giuseppe Panuccio, Carlo Ferravante, Giorgio Giurato, Francesca Rizzo, Michele Torella, Maria Donniacuo, Antonella De Angelis, Giuseppe Viglietto, Konrad Urbanek, Alessandro Weisz, Daniele Torella and Eleonora Cianfloneadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2023, 24(2), 1132; https://doi.org/10.3390/ijms24021132 - 6 Jan 2023
Cited by 32 | Viewed by 10481
Abstract
The main cause of morbidity and mortality in diabetes mellitus (DM) is cardiovascular complications. Diabetic cardiomyopathy (DCM) remains incompletely understood. Animal models have been crucial in exploring DCM pathophysiology while identifying potential therapeutic targets. Streptozotocin (STZ) has been widely used to produce experimental [...] Read more.
The main cause of morbidity and mortality in diabetes mellitus (DM) is cardiovascular complications. Diabetic cardiomyopathy (DCM) remains incompletely understood. Animal models have been crucial in exploring DCM pathophysiology while identifying potential therapeutic targets. Streptozotocin (STZ) has been widely used to produce experimental models of both type 1 and type 2 DM (T1DM and T2DM). Here, we compared these two models for their effects on cardiac structure, function and transcriptome. Different doses of STZ and diet chows were used to generate T1DM and T2DM in C57BL/6J mice. Normal euglycemic and nonobese sex- and age-matched mice served as controls (CTRL). Immunohistochemistry, RT-PCR and RNA-seq were employed to compare hearts from the three animal groups. STZ-induced T1DM and T2DM affected left ventricular function and myocardial performance differently. T1DM displayed exaggerated apoptotic cardiomyocyte (CM) death and reactive hypertrophy and fibrosis, along with increased cardiac oxidative stress, CM DNA damage and senescence, when compared to T2DM in mice. T1DM and T2DM affected the whole cardiac transcriptome differently. In conclusion, the STZ-induced T1DM and T2DM mouse models showed significant differences in cardiac remodeling, function and the whole transcriptome. These differences could be of key relevance when choosing an animal model to study specific features of DCM. Full article
(This article belongs to the Special Issue Effects of Dyslipidemia and Metabolic Syndrome on Cardiac and Vascular Dysfunction)
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Review

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41 pages, 621 KiB  
Review
Atherosclerosis, Diabetes Mellitus, and Cancer: Common Epidemiology, Shared Mechanisms, and Future Management
by Vasiliki Katsi, Ilias Papakonstantinou and Konstantinos Tsioufis
Int. J. Mol. Sci. 2023, 24(14), 11786; https://doi.org/10.3390/ijms241411786 - 22 Jul 2023
Cited by 10 | Viewed by 3307
Abstract
The involvement of cardiovascular disease in cancer onset and development represents a contemporary interest in basic science. It has been recognized, from the most recent research, that metabolic syndrome-related conditions, ranging from atherosclerosis to diabetes, elicit many pathways regulating lipid metabolism and lipid [...] Read more.
The involvement of cardiovascular disease in cancer onset and development represents a contemporary interest in basic science. It has been recognized, from the most recent research, that metabolic syndrome-related conditions, ranging from atherosclerosis to diabetes, elicit many pathways regulating lipid metabolism and lipid signaling that are also linked to the same framework of multiple potential mechanisms for inducing cancer. Otherwise, dyslipidemia and endothelial cell dysfunction in atherosclerosis may present common or even interdependent changes, similar to oncogenic molecules elevated in many forms of cancer. However, whether endothelial cell dysfunction in atherosclerotic disease provides signals that promote the pre-clinical onset and proliferation of malignant cells is an issue that requires further understanding, even though more questions are presented with every answer. Here, we highlight the molecular mechanisms that point to a causal link between lipid metabolism and glucose homeostasis in metabolic syndrome-related atherosclerotic disease with the development of cancer. The knowledge of these breakthrough mechanisms may pave the way for the application of new therapeutic targets and for implementing interventions in clinical practice. Full article
(This article belongs to the Special Issue Effects of Dyslipidemia and Metabolic Syndrome on Cardiac and Vascular Dysfunction)
14 pages, 1127 KiB  
Review
Effects of Hypoglycemia on Cardiovascular Function in Patients with Diabetes
by Maria A. Christou, Panagiota A. Christou, Christos Kyriakopoulos, Georgios A. Christou and Stelios Tigas
Int. J. Mol. Sci. 2023, 24(11), 9357; https://doi.org/10.3390/ijms24119357 - 27 May 2023
Cited by 9 | Viewed by 6597
Abstract
Hypoglycemia is common in patients with type 1 and type 2 diabetes (T1D, T2D), treated with insulin or sulfonylureas, and has multiple short- and long-term clinical implications. Whether acute or recurrent, hypoglycemia significantly affects the cardiovascular system with the potential to cause cardiovascular [...] Read more.
Hypoglycemia is common in patients with type 1 and type 2 diabetes (T1D, T2D), treated with insulin or sulfonylureas, and has multiple short- and long-term clinical implications. Whether acute or recurrent, hypoglycemia significantly affects the cardiovascular system with the potential to cause cardiovascular dysfunction. Several pathophysiological mechanisms have been proposed linking hypoglycemia to increased cardiovascular risk, including hemodynamic changes, myocardial ischemia, abnormal cardiac repolarization, cardiac arrhythmias, prothrombotic and proinflammatory effects, and induction of oxidative stress. Hypoglycemia-induced changes can promote the development of endothelial dysfunction, which is an early marker of atherosclerosis. Although data from clinical trials and real-world studies suggest an association between hypoglycemia and cardiovascular events in patients with diabetes, it remains uncertain whether this association is causal. New therapeutic agents for patients with T2D do not cause hypoglycemia and have cardioprotective benefits, whereas increasing the use of new technologies, such as continuous glucose monitoring devices and insulin pumps, has the potential to reduce hypoglycemia and its adverse cardiovascular outcomes in patients with T1D. Full article
(This article belongs to the Special Issue Effects of Dyslipidemia and Metabolic Syndrome on Cardiac and Vascular Dysfunction)
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14 pages, 1612 KiB  
Review
Caveolin-1 and Atherosclerosis: Regulation of LDLs Fate in Endothelial Cells
by Alessandra Puddu, Fabrizio Montecucco and Davide Maggi
Int. J. Mol. Sci. 2023, 24(10), 8869; https://doi.org/10.3390/ijms24108869 - 17 May 2023
Cited by 6 | Viewed by 2381
Abstract
Caveolae are 50–100 nm cell surface plasma membrane invaginations observed in terminally differentiated cells. They are characterized by the presence of the protein marker caveolin-1. Caveolae and caveolin-1 are involved in regulating several signal transduction pathways and processes. It is well recognized that [...] Read more.
Caveolae are 50–100 nm cell surface plasma membrane invaginations observed in terminally differentiated cells. They are characterized by the presence of the protein marker caveolin-1. Caveolae and caveolin-1 are involved in regulating several signal transduction pathways and processes. It is well recognized that they have a central role as regulators of atherosclerosis. Caveolin-1 and caveolae are present in most of the cells involved in the development of atherosclerosis, including endothelial cells, macrophages, and smooth muscle cells, with evidence of either pro- or anti-atherogenic functions depending on the cell type examined. Here, we focused on the role of caveolin-1 in the regulation of the LDLs’ fate in endothelial cells. Full article
(This article belongs to the Special Issue Effects of Dyslipidemia and Metabolic Syndrome on Cardiac and Vascular Dysfunction)
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