Search Results (252)

Diabetic wounds are a devastating complication that cause chronic pain, recurrent infections, and limb amputations due to impaired healing. Despite advances in wound care, existing therapies often fail to address the underlying molecular dysregulation, highlighting the need for innovative and safe therapeutic approaches. Among these, D-amino acids such as D-tryptophan (D-Trp) have emerged as key regulators of cellular processes; however, their therapeutic potential in diabetic wounds remains largely unexplored. Here, we investigate the therapeutic potential of D-Trp in streptozotocin (STZ)-induced diabetic mice, comparing it with phosphate-buffered saline (PBS) controls and vascular endothelial growth factor (VEGF) as a positive control. Wound healing, inflammation, and histopathology were assessed. Protein and gene expression were analyzed via Western blot and RT-qPCR, respectively. Biolayer interferometry (BLI) measured the binding of D-Trp to hypoxia-inducible factor-1α (HIF-1α). D-Trp accelerated wound healing by modulating extracellular matrix (ECM) remodeling, signaling, and apoptosis. It upregulated matrix metalloproteinases (MMP1, MMP3, MMP-9), Janus kinase 2 (JAK2), and mitogen-activated protein kinase (MAPK) proteins while reducing pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], IL-6). D-Trp also suppressed caspase-3 and enhanced angiogenesis through HIF-1α activation. These findings suggest that D-Trp promotes healing by boosting ECM turnover, reducing inflammation, and activating MAPK/JAK pathways. Thus, D-Trp is a promising therapeutic for diabetic wounds. Full article

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease characterized by chronic inflammation, vascular remodeling, and immune dysregulation. COVID-19, caused by SARS-CoV-2, shares several systemic immunohematologic disturbances with IPF, including cytokine storms, endothelial injury, and prothrombotic states. Unlike general comparisons of viral infections and chronic lung disease, this review offers a focused analysis of the shared hematologic and immunologic mechanisms between COVID-19 and IPF. Our aim is to better understand how SARS-CoV-2 infection may worsen disease progression in IPF and identify converging pathophysiological pathways that may inform clinical management. We conducted a narrative synthesis of the peer-reviewed literature from PubMed, Scopus, and Web of Science, focusing on clinical, experimental, and pathological studies addressing immune and coagulation abnormalities in both COVID-19 and IPF. Both diseases exhibit significant overlap in inflammatory and fibrotic signaling, particularly via the TGF-β, IL-6, and TNF-α pathways. COVID-19 amplifies coagulation disturbances and endothelial dysfunction already present in IPF, promoting microvascular thrombosis and acute exacerbations. Myeloid cell overactivation, impaired lymphocyte responses, and fibroblast proliferation are central to this shared pathophysiology. These synergistic mechanisms may accelerate fibrosis and increase mortality risk in IPF patients infected with SARS-CoV-2. This review proposes an integrative framework for understanding the hematologic and immunologic convergence of COVID-19 and IPF. Such insights are essential for refining therapeutic targets, improving prognostic stratification, and guiding early interventions in this high-risk population. Full article

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive form of pre-capillary pulmonary hypertension characterized by persistent, organized thromboemboli in the pulmonary vasculature, leading to vascular remodeling, elevated pulmonary artery pressures, right heart failure, and significant morbidity and mortality if untreated. Despite advances, CTEPH remains underdiagnosed due to nonspecific symptoms and overlapping features with other forms of pulmonary hypertension. Basic Methodology: This review synthesizes data from large international registries, epidemiologic studies, translational research, and multicenter clinical trials. Key methodologies include analysis of registry data to assess incidence and risk factors, histopathological examination of lung specimens, and molecular studies investigating endothelial dysfunction and inflammatory pathways. Diagnostic modalities and treatment outcomes are evaluated through observational studies and randomized controlled trials. Recent Advances and Affected Population: Research has elucidated that CTEPH arises from incomplete resolution of pulmonary emboli, with subsequent fibrotic transformation mediated by dysregulated TGF-β/TGFBI signaling, endothelial dysfunction, and chronic inflammation. Affected populations are typically older adults, often with prior venous thromboembolism, splenectomy, or prothrombotic conditions, though up to 25% have no history of acute PE. The disease burden is substantial, with delayed diagnosis contributing to worse outcomes and higher societal costs. Microvascular arteriopathy and PAH-like lesions in non-occluded vessels further complicate the clinical picture. Conclusions: CTEPH is now recognized as a treatable disease, with multimodal therapies—surgical endarterectomy, balloon pulmonary angioplasty, and targeted pharmacotherapy—significantly improving survival and quality of life. Ongoing research into molecular mechanisms and biomarker-driven diagnostics promises earlier identification and more personalized management. Multidisciplinary care and continued translational investigation are essential to further reduce mortality and optimize outcomes for this complex patient population. Full article

Background/Objective: Pulmonary fungal infections are a significant diagnostic challenge, primarily affecting immunocompromised individuals, such as those with HIV, cancer, or organ transplants, and they often lead to substantial morbidity and mortality if untreated. These infections trigger acute inflammatory and immune responses, which may progress to chronic inflammation. This process involves myofibroblast recruitment, the deposition of extracellular matrix, and vascular remodeling, ultimately contributing to pulmonary hypertension. Despite its clinical relevance, pulmonary hypertension secondary to fungal infections remains under-recognized in practice and poorly studied in research. Results/Conclusion: This narrative mini-review explores three key mechanisms underlying vascular remodeling in this context: (1) endothelial injury caused by fungal emboli or autoimmune reactions, (2) direct vascular remodeling during chronic infection driven by inflammation and fibrosis, and (3) distant vascular remodeling post-infection, as seen in granulomatous diseases like paracoccidioidomycosis. Further research and clinical screening for pulmonary hypertension in fungal infections are crucial to improving patient outcomes. Full article

Plantar fasciitis is a common condition characterized by inflammation and degeneration of the plantar fascia, leading to heel pain and reduced mobility. Affecting both athletic and non-athletic populations, it is a leading cause of foot-related medical visits. Conservative treatments, including rest, physical therapy, and corticosteroid injections, provide relief for most patients, but a subset experiences persistent symptoms requiring advanced therapies. Emerging biologic treatments, such as platelet-rich plasma (PRP) and mesenchymal stem/stromal cell (MSC) therapy, have demonstrated potential in promoting tissue regeneration and reducing inflammation. Recently, MSC-derived extracellular vesicles (MSC-EVs) have gained attention for their regenerative properties, offering a promising, cell-free therapeutic approach. EVs mediate tissue repair through immunomodulation, anti-inflammatory signaling, and extracellular matrix stabilization. Preclinical studies suggest that EV therapy may improve tendon and ligament healing by promoting M2 macrophage polarization, inhibiting excessive metalloproteinase activity, and enhancing vascular remodeling. This review explores the potential of MSC-EVs as an innovative, non-surgical treatment for plantar fasciitis, addressing their mechanisms of action and current evidence in musculoskeletal regeneration. Full article

Cardiovascular injury caused by fine particulate matter (PM2.5) exposure is an escalating public health concern due to its role in triggering systemic inflammation and oxidative stress. This study elucidates the sirtuin 1 (SIRT1)-mediated epigenetic mechanisms underlying the protective effects of phytosome-encapsulated Zea mays L. var. ceratina tassel extract (PZT) in a rat model of PM2.5-induced cardiovascular inflammation. Male Wistar rats were pretreated with PZT (100, 200, and 400 mg/kg body weight) for 21 days before and throughout a 27-day PM2.5 exposure period. SIRT1 expression and associated inflammatory and oxidative stress markers were evaluated in cardiac and vascular tissues. The findings revealed that PZT significantly upregulated SIRT1 expression, a key epigenetic regulator known to modulate inflammatory and antioxidant pathways. The activation of SIRT1 inhibited the nuclear factor-kappa B (NF-κB) signaling pathway, leading to a reduction in pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) within cardiac tissue. In vascular tissue, treatment with PZT reduced the levels of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β), thereby mitigating inflammatory and fibrotic responses. Furthermore, SIRT1 activation by PZT enhanced the antioxidant defense system by upregulating superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), which was associated with a decrease in malondialdehyde (MDA), a marker of lipid peroxidation. Collectively, these results demonstrate that PZT confers cardiovascular protection through SIRT1-dependent epigenetic modulation, mitigating PM2.5-induced inflammation, oxidative stress, and tissue remodeling. The dual anti-inflammatory and antioxidant actions of PZT via SIRT1 activation highlight its potential as a functional food-based preventative agent for reducing cardiovascular risk in polluted environments. Full article

The evolution of percutaneous coronary intervention (PCI) has led to significant advances in drug-coated balloon (DCB) technology, offering a stent-free alternative for treating coronary artery disease. While paclitaxel-coated balloons (PCBs) have been the standard, sirolimus-coated balloons (SCBs) are emerging as a viable alternative with distinct pharmacokinetic and clinical benefits. This review explores the mechanisms of action of paclitaxel and sirolimus, their impact on different plaque morphologies, and the clinical implications of DCB selection. Paclitaxel facilitates positive vascular remodeling and is particularly effective in fibrotic and lipid-rich plaques, but its poor penetration in calcified lesions remains a limitation. Sirolimus, with its homogeneous tissue distribution and anti-inflammatory properties, is better suited for unstable, lipid-rich, and inflammatory plaques, where it promotes plaque stabilization. Recent randomized trials and meta-analyses have compared SCBs vs. PCBs in both de novo lesions and in-stent restenosis, showing non-inferior outcomes. Additionally, DCBs demonstrate comparable efficacy to DES in small vessel disease, reducing the need for permanent metallic scaffolds. This review summarizes the current evidence on DCB selection based on plaque characteristics and highlights areas for further investigation in personalized PCI strategies. Given the narrative review design, the authors conducted a comprehensive literature search using databases such as PubMed and MEDLINE. Keywords included “drug-coated balloon”, “paclitaxel-coated balloon”, “sirolimus-coated balloon”, “in-stent restenosis”, and “plaque morphology”. Studies were selected based on relevance, including randomized controlled trials, registries, and meta-analyses. No formal inclusion/exclusion criteria or systematic screening were applied due to the nature of narrative synthesis. Full article

Galectin-1 (Gal-1), a β-galactoside-binding lectin, plays a complex role in cardiovascular diseases (CVDs), exerting both protective and pathological effects depending on the context. This review synthesizes findings from the past decade to explore Gal-1’s involvement in key aspects of CVD pathogenesis, including vascular homeostasis, inflammation regulation, atherosclerosis progression, myocardial remodeling, and heart failure. While Gal-1 supports endothelial integrity and immune modulation, its dysregulation contributes to disease progression through pro-inflammatory signaling, fibrosis, and adverse cardiac remodeling. Emerging evidence suggests that Gal-1 holds potential as both a biomarker for risk assessment and a therapeutic target. However, critical knowledge gaps remain, particularly regarding its context-dependent effects, the limited scope of clinical trials, and unresolved mechanistic insights. Addressing these challenges will be essential to fully harness Gal-1’s therapeutic potential in cardiovascular medicine, guiding future research efforts toward precision interventions and clinical applications. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) pandemic that devastated the world. While this is a respiratory virus, one feature of the SARS-CoV-2 infection was recognized to cause pathogenesis of other organs. Because the membrane fusion protein of SARS-CoV-2, the spike protein, binds to its major host cell receptor angiotensin-converting enzyme 2 (ACE2), which regulates a critical mediator of cardiovascular diseases, angiotensin II, COVID-19 is largely associated with vascular pathologies. The present study examined the pulmonary vasculature of COVID-19 patients using large sample sizes and provides mechanistic information through histological observations. We studied 56 postmortal lung samples from COVID-19 patients. The comparative group consisted of 17 postmortal lung samples from patients who died of influenza A virus subtype H1N1. The examination of 56 autopsy lung samples showed thickened vascular walls of small pulmonary arteries after 14 days of disease compared to H1N1 influenza patients who died before the COVID-19 pandemic started. Pulmonary vascular remodeling in COVID-19 patients was associated with hypertrophy of the smooth muscle layer, perivascular fibrosis, edema and lymphostasis, inflammatory infiltration, perivascular hemosiderosis, and neoangiogenesis. We found a correlation between the duration of hospital stay and the thickness of the muscular layer of the pulmonary arterial walls. These results demonstrate that COVID-19 significantly affected the pulmonary vasculature in fatal-course patients, also suggesting the need for careful follow-up in non-fatal cases, at risk of pulmonary hypertension. Full article

Background and Objectives: Maternal dyslipidaemia and low-grade inflammation are recognised drivers of in utero vascular remodelling, yet composite dynamic markers that integrate lipid–glycaemic, inflammatory and endothelial signals have not been evaluated. We investigated whether eight-week trajectories in the triglyceride–glucose index (TyG), interleukin-6 (IL-6) and flow-mediated dilation (FMD) outperform single-timepoint lipids for predicting fetal aortic remodelling. Materials and Methods: In a prospective repeated-measures study, 90 singleton pregnancies were examined at 24–26 weeks (Visit-1) and 32–34 weeks (Visit-2). At each visit, we obtained fasting lipids, TyG index, hsCRP, IL-6, oxidative-stress markers (MDA, NOx), brachial flow-mediated dilation (FMD), carotid IMT and uterine-artery Doppler, together with advanced fetal ultrasonography (abdominal-aorta IMT, ventricular strain, Tei-index, fetal pulse-wave velocity). Mothers were grouped by k-means clustering of the visit-to-visit change (Δ) in TG, TyG, hsCRP, IL-6 and FMD into three Metabolic-Inflammatory Response Phenotypes (MIRP-1/2/3). Linear mixed-effects models and extreme-gradient-boosting quantified associations and predictive performance. Results: Mean gestational TG rose from 138.6 ± 14.1 mg/dL to 166.9 ± 15.2 mg/dL, TyG by 0.21 ± 0.07 units and FMD fell by 1.86 ± 0.45%. MIRP-3 (“Metabolic + Inflammatory”; n = 31) showed the largest change (Δ) Δ-hsCRP (+0.69 mg/L) and Δ-FMD (–2.8%) and displayed a fetal IMT increase of +0.17 ± 0.05 mm versus +0.07 ± 0.03 mm in MIRP-1 (p < 0.001). Mixed-effects modelling identified Δ-TyG (β = +0.054 mm per unit), Δ-IL-6 (β = +0.009 mm) and Δ-FMD (β = –0.007 mm per %) as independent determinants of fetal IMT progression. An XGBoost model incorporating these Δ-variables predicted high fetal IMT (≥90th percentile) with AUROC 0.88, outperforming logistic regression (AUROC 0.74). Conclusions: A short-term surge in maternal TyG, IL-6 and endothelial dysfunction delineates a high-risk phenotype that doubles fetal aortic wall thickening and impairs myocardial performance. Composite dynamic indices demonstrated superior predictive value compared with individual lipid markers. Full article

Background: Arteriovenous fistula (AVF) failure rates are consistently higher in females, although the underlying mechanisms remain incompletely understood. Inflammatory processes play a key role in AVF remodeling and venous arterialization, yet their influence may differ by sex. This study aimed to evaluate the impact of inflammatory indices on AVF blood flow and maturation, with a focus on sex-specific differences. Methods: This retrospective analytical study included 110 patients (50 females, 60 males) undergoing initial surgical AVF creation. Postoperative assessments occurred at the fourth and sixth weeks. Patients demonstrating insufficient maturation (blood flow < 600 mL/min) at the fourth week were re-evaluated after two weeks without any intervening procedures or additional interventions. Results: Intraoperative Transit-Time Flow Measurement (TTFM) revealed significantly higher median AVF blood flow in males compared to females (289 mL/min vs. 200 mL/min; p < 0.001). Doppler ultrasonography (DUS) findings confirmed these sex-related differences, demonstrating consistently lower blood flow rates in female patients. An elevated neutrophil-to-lymphocyte ratio (NLR) was associated with approximately a 31% reduction in AVF blood flow among females, whereas an increased C-reactive protein-to-albumin ratio (CrA) correlated with an approximate 9% decline. In males, an elevated systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) were significantly associated with decreased AVF blood flow. Conversely, a higher prognostic nutritional index (PNI) positively correlated with AVF blood flow in both sexes. Risk factors associated with inadequate AVF maturation (<600 mL/min at sixth week) included female sex, advanced age, obesity, smoking, anemia, low vitamin D levels, and elevated inflammatory indices (NLR, SII, and SIRI). Conclusions: Inflammatory and nutritional indices derived from routine laboratory tests may assist in estimating AVF maturation likelihood. While DUS reliably assesses AVF blood flow, complementary evaluation methods may be required to assess the broader vascular status. Further research is needed to clarify sex-specific inflammatory mechanisms influencing AVF outcomes and to guide individualized management strategies. Full article

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is characterized by chronic intestinal inflammation and impaired epithelial barrier function. Emerging evidence highlights the critical role of vascular remodeling and angiogenesis in IBD pathogenesis. This review explores the intricate relationship between blood vessels and the intestinal epithelial barrier, emphasizing how aberrant vascularization contributes to barrier dysfunction and disease progression. In IBD, excessive angiogenesis is driven by hypoxia, immune cell infiltration, and pro-inflammatory cytokines, further perpetuating inflammation and tissue damage. Key angiogenic factors, such as vascular endothelial growth factor (VEGF), angiopoietins, and platelet-derived growth factor (PDGF), are upregulated in IBD, promoting pathological vessel formation. These newly formed vessels are often immature and hyperpermeable, exacerbating leukocyte recruitment and inflammatory responses. Given the pivotal role of angiogenesis in IBD, anti-angiogenic therapies have emerged as a potential therapeutic strategy. Preclinical and clinical studies targeting VEGF and other angiogenic pathways have shown promise in reducing inflammation and promoting mucosal healing. This review summarizes current knowledge on vascular–epithelial interactions in IBD, the mechanisms driving pathological angiogenesis, and the therapeutic potential of anti-angiogenic approaches, providing insights for future research and treatment development. Full article

Pulmonary hypertension (PH) is a serious cardiovascular disease caused by a variety of pathogenic factors, which is characterized by increased pulmonary vascular resistance (PVR) and progressive elevation of mean pulmonary artery pressure (mPAP). This disease can lead to right ventricular hypertrophy and, in severe cases, right heart failure and even death. Vascular remodeling—a pathological modification involving aberrant vasoconstriction, cell proliferation, apoptosis resistance, and inflammation in the pulmonary vascular system—is a significant pathological hallmark of PH and a critical process in its progression. Recent studies have found that vascular remodeling involves the participation of a diversity of cellular pathological alterations, such as the dysfunction of pulmonary artery endothelial cells (PAECs), the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs), the phenotypic differentiation of pulmonary artery fibroblasts, the inflammatory response of immune cells, and pericyte proliferation. This review focuses on the mechanisms and the intercellular crosstalk of these cells in the PH process, emphasizing recent advances in knowledge regarding cellular signaling pathways, inflammatory responses, apoptosis, and proliferation. To develop better treatments, a list of possible therapeutic approaches meant to slow down certain biological functions is provided, with the aim of providing new insights into the treatment of PH by simplifying the intricacies of these complex connections. In this review, comprehensive academic databases such as PubMed, Embase, Web of Science, and Google Scholar were systematically searched to discuss studies relevant to human and animal PH, with a focus on vascular remodeling in PH. Full article

Objectives: Tissue factor pathway inhibitor 2 (TFPI2) is a serine protease inhibitor that suppresses tumors by preventing extracellular matrix degradation and invasion. In many malignancies, the TFPI2 promoter hypermethylation silences its transcription, increasing tumor aggressiveness. However, TFPI2 paradoxically facilitates tumor progression in certain malignancies. Elevated circulating TFPI2 levels correlate with increased cancer aggressiveness and poor prognosis in ovarian, endometrial, and renal cell carcinoma, though the mechanisms underlying its tumor-promoting effects remain unclear. This review consolidates recent findings on TFPI2 regulation, its downstream targets in cellular homeostasis, and its prognostic significance. Additionally, we reassess TFPI2′s role in tumorigenesis, particularly in clear cell carcinoma, as well as in chronic inflammation. Methods: A comprehensive literature search was performed in PubMed and Google Scholar without time restriction. Results: TFPI2 expression is tightly regulated by transcription factors, signaling molecules, growth factors, cytokines, and epigenetic modification. TFPI2 regulates cell proliferation, inflammation, and extracellular matrix (ECM) remodeling, preserving tissue homeostasis. TFPI2 also regulates vascular endothelial and smooth muscle cell proliferation, key elements of the tumor microenvironment (TME). In the nucleus, it may modulate transcription factors to influence tumor-associated macrophage (TAM) polarization, facilitating cancer invasion. Its expression may be shaped by interactions between cancer cells and TAM activation. Beyond tumorigenesis, TFPI2 contributes to both inflammatory progression and resolution in diabetes, atherosclerosis, and preeclampsia. Conclusions: TFPI2 may interact with TAMs and inflammatory cells to regulate cell proliferation and inflammation, maintaining tissue homeostasis. Full article

Chronic venous disease (CVD) involves complex pathophysiological mechanisms, particularly an imbalance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), contributing to venous remodeling and varicosities. Elevated MMP-2 and MMP-9 levels are commonly found in tissues affected by venous ulcers. Inflammation plays a central role in CVD, with higher levels of pro-inflammatory markers present in varicose veins compared to healthy ones. Syndecans, key components of the endothelial glycocalyx, are involved in inflammatory responses. Alterations in the glycocalyx structure are associated with vascular damage in both venous and arterial diseases. This study aimed to investigate inflammatory changes in CVD patients, focusing on glycocalyx damage and the therapeutic role of mesoglycan, a glycosaminoglycan-based drug. A prospective, monocentric study included 23 patients with C2 clinical–etiological–anatomical–pathological (CEAP) CVD. Serum samples were collected before and after mesoglycan treatment. Results showed significantly elevated levels of VCAM-1, MMP-2, MMP-9, SDC-1, IL-6, and IL-8 in blood from varicose veins versus the systemic circulation. Patients received 50 mg of mesoglycan orally every 12 h for 90 days. After treatment, a notable reduction in inflammatory markers was observed. These results support the hypothesis that mesoglycan may alleviate both local and systemic inflammation, providing insights into new therapeutic strategies for CVD management. Full article