Search Results (214)

Atherosclerosis (AS), a progressive inflammatory disease of coronary arteries, the aorta, and the internal carotid artery, is considered one of the main contributors to cardiovascular disorders. Blood flow is restricted by accumulating lipid-rich macrophages (foam cells), calcium, fibrin, and cellular debris into plaques on the intima of arterial walls. Butyrate maintains gut barrier integrity and modulates immune responses. Butyrate regulates G-protein-coupled receptor (GPCR) signaling and activates nuclear factor kappa-B (NF-κB), activator protein-1 (AP-1), and interferon regulatory factors (IFRs) involved in the production of proinflammatory cytokines. Depending on the inflammatory stimuli, butyrate may also inactivate NF-κB, resulting in the suppression of proinflammatory cytokines and the stimulation of anti-inflammatory cytokines. Butyrate modulates mitogen-activated protein kinase (MAPK) to promote or suppress macrophage inflammation, muscle cell growth, apoptosis, and the uptake of oxidized low-density lipoprotein (ox-LDL) in macrophages. Activation of the peroxisome proliferator-activated receptor γ (PPARγ) pathway plays a role in lipid metabolism, inflammation, and cell differentiation. Butyrate inhibits interferon γ (IFN-γ) signaling and suppresses NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) involved in inflammation and scar tissue formation. The dual role of butyrate in AS is discussed by addressing the interactions between butyrate, intestinal epithelial cells (IECs), endothelial cells (ECs) of the main arteries, and immune cells. Signals generated from these interactions may be applied in the diagnosis and intervention of AS. Reporters to detect early AS is suggested. This narrative review covers the most recent findings published in PubMed and Crossref databases. Full article

Vein graft restenosis remains a major complication following coronary artery bypass grafting (CABG), mainly due to the abnormal proliferation of vascular smooth muscle cells (VSMCs) and impaired endothelial repair. While external stents (eStents) can provide mechanical support and limit adverse remodeling, traditional metallic stents are non-degradable and may induce chronic inflammation and fibrosis. In contrast, many bioresorbable materials degrade too quickly or lack mechanical strength. These challenges highlight the need for external stents that combine sufficient mechanical strength with biodegradability to support long-term graft patency. This is the first study that develops a chlorogenic acid–strontium (SrCA)-loaded polycaprolactone bioresorbable eStent that inhibits VSMC proliferation and enhances endothelial repair via Hippo–Yes-associated protein (YAP) signaling, addressing vein graft restenosis post-CABG. Combining mechanical support and biodegradability, it overcomes the limitations of non-degradable stents and rapidly degrading biomaterials, elucidates the potential of natural polyphenol–metal ion complexes in vascular remodeling, and offers an innovative strategy for the prevention of vein graft restenosis. Full article

Poloxamer (P) 188 attenuates myocardial ischemia/reperfusion injury through cell membrane stabilization. Cell–cell interactions between endothelial cells (ECs) and cardiomyocytes (CMs) further protect CMs: co-cultures showed that, at an optimal density, ECs protected CMs against hypoxia/reoxygenation (HR) injury. The mechanism of interaction with P188 still requires exploration. We examined if N(ω)-nitro-L-arginine methyl ester (LNAME), a non-specific nitric oxide (NO) synthase inhibitor, abolishes protection in the presence or absence of P188 and/or ECs. We co-cultured mouse coronary artery ECs in an insert atop mouse CMs plated at confluency on the bottom of a well. Normoxic controls remained in complete media while HR groups were exposed to 24 h hypoxia at 0.01% O₂ in serum- and glucose-free media, followed by 2 h reoxygenation in complete media. P188 (300 μM), LNAME (40 mM), or vehicle were administered upon reoxygenation. ECs at the used lower density did not decrease HR-triggered lactate dehydrogenase release or calcium overload in CMs by themselves. P188 reduced both indicators after HR by 16/18% without and by 22/25% with ECs, respectively. LNAME abrogated CM protection by P188. Neither intervention had an effect under normoxia. Our co-culture data indicates that P188 requires NO, not necessarily of endothelial origin, to elicit CM protection. Full article

Background/Objectives: Patients with chronic kidney disease (CKD) are associated with a significantly elevated cardiovascular risk. The incidence and prevalence of mediated cardiac disorders and major adverse cardiac events (MACEs), such as heart failure, arrhythmias, acute coronary syndrome (ACS) based on coronary artery disease (CAD), stroke, venous thromboembolism, and peripheral artery disease, are significantly higher in CKD patients as compared with the general population. Methods: This narrative review summarizes the current clinical understanding, the pathophysiological mechanisms, and the clinical consequences in the context of cardiovascular risk and disease in CKD. Results: The impact of CKD on mediated cardiovascular disorders and elevated MACE prevalence is complex and multifactorial. The underlying mechanisms involve various traditional cardiovascular risk factors, such as arterial hypertension, smoking, dyslipidemia, and diabetes. Furthermore, CKD-specific molecular and pathophysiological factors, such as chronic inflammation and associated oxidative stress and endothelial cell dysfunction, pro-coagulatory status, uremic toxins and uremic lipids, progressive vascular calcification, and alterations in the regulation of the renin–angiotensin–aldosterone system (RAAS) and sympathetic activation cause an increased cardiovascular risk. Conclusions: Understanding the complex disease mechanisms between CKD and elevated cardiovascular risk might contribute to optimizing individual patients’ risk stratification and result in individualized diagnostic and treatment strategies via appropriate clinical biomarker application and individualized anti-inflammatory approaches. Full article

Calcium (Ca²⁺) signaling is a fundamental regulatory mechanism controlling essential processes in the endothelium, vascular smooth muscle cells (VSMCs), and the extracellular matrix (ECM), including maintaining the endothelial barrier, modulation of vascular tone, and vascular remodeling. Cytosolic free Ca²⁺ concentration is tightly regulated by a balance between Ca²⁺ mobilization mechanisms, including Ca²⁺ release from the intracellular stores in the sarcoplasmic/endoplasmic reticulum and Ca²⁺ entry via voltage-dependent, transient-receptor potential, and store-operated Ca²⁺ channels, and Ca²⁺ elimination pathways including Ca²⁺ extrusion by the plasma membrane Ca²⁺-ATPase and Na⁺/Ca²⁺ exchanger and Ca²⁺ re-uptake by the sarco(endo)plasmic reticulum Ca²⁺-ATPase and the mitochondria. Some cell membranes/organelles are multifunctional and have both Ca²⁺ mobilization and Ca²⁺ removal pathways. Also, the individual Ca²⁺ handling pathways could be integrated to function in a regenerative, capacitative, cooperative, bidirectional, or reciprocal feed-forward or feed-back manner. Disruption of these pathways causes dysregulation of the Ca²⁺ signaling dynamics and leads to pathological cardiovascular conditions such as hypertension, coronary artery disease, atherosclerosis, and vascular calcification. In the endothelium, dysregulated Ca²⁺ signaling impairs nitric oxide production, reduces vasodilatory capacity, and increases vascular permeability. In VSMCs, Ca²⁺-dependent phosphorylation of the myosin light chain and Ca²⁺ sensitization by protein kinase-C (PKC) and Rho-kinase (ROCK) increase vascular tone and could lead to increased blood pressure and hypertension. Ca²⁺ activation of matrix metalloproteinases causes collagen/elastin imbalance and promotes vascular remodeling. Ca²⁺-dependent immune cell activation, leukocyte infiltration, and cholesterol accumulation by macrophages promote foam cell formation and atherosclerotic plaque progression. Chronic increases in VSMCs Ca²⁺ promote phenotypic switching to mesenchymal cells and osteogenic transformation and thereby accelerate vascular calcification and plaque instability. Emerging therapeutic strategies targeting these Ca²⁺-dependent mechanisms, including Ca²⁺ channel blockers and PKC and ROCK inhibitors, hold promise for restoring Ca²⁺ homeostasis and mitigating vascular disease progression. Full article

Background: Cardiovascular disorders, especially atherosclerosis, have been associated with allergic inflammation. In addition to traditional inflammatory responses, there is evidence that the development and instability of coronary artery plaque may be influenced by effector cells of allergic inflammation. This review examines the phases of allergic pathology, the immunological mechanisms of atherosclerosis, and the clinical link between allergic diseases (asthma, atopic dermatitis, allergic rhinitis, and food allergy) and cardiovascular disease (CVD), along with future therapeutic perspectives. Material and Method: A literature search was conducted in PubMed, Google scholar; ScienceDirect, Scopus, and studies published between 2014–2024 were taken into consideration. Keywords included allergic inflammation, eosinophils, mast cells, reactive oxygen species, atherosclerosis, Th2 cells, and cytokines. Epidemiological studies and review articles were included. Results: Emerging evidence suggests that allergic inflammation contributes to atherosclerosis through interconnected mechanisms such as eosinophil activation, reactive oxygen species production, mast cell degranulation, and endothelial dysfunction. Th2-driven immune responses, which are mediated by cytokines such as IL-4, IL-5, and IL-13, as well as eosinophil activity and mast cell degranulation, play a crucial role in vascular inflammation and plaque progression. Additionally, changes in lipid metabolism contribute to this process. Epidemiological studies support this connection, indicating that patients with chronic allergic conditions such as asthma, allergic rhinitis, food allergy, and atopic dermatitis experience increased cardiovascular morbidity. However, most current data are observational, and our understanding of the underlying mechanisms in humans remains limited, often relying on insights gained from preclinical models. Conclusions: A potential mechanism for cardiovascular risk is suggested by the interaction between atherosclerosis and allergic inflammation. Promising alternatives for treating allergic inflammation and cardiovascular issues include novel treatments like cytokine inhibitors, mast cell stabilizers, and biologics that target certain pathways. Further research is necessary to see whether concentrating on allergy pathways could lead to innovative treatments for cardiovascular disorders or vice versa. Full article

In atherosclerosis, the proliferation and migration of endothelial and smooth muscle cells (SMCs) and platelet activation alter endothelial function. Naturally occurring substances, such as caffeic acid (CA) and Trametes versicolor extract (TvE), have medicinal properties and are traditionally used for their antiproliferative, antioxidant, and anti-inflammatory effects. Electrospun 5% and 8% polycaprolactone-loaded CA or TvE was developed as a delivery system. Cytocompatibility was evaluated using human coronary artery endothelial cells (HCAECs), coronary artery SMCs (CASMCs), and platelets. Three types of systems (µF-CA, µF-TvE, and µF-CA/TvE) were developed and microscopically characterized. Analysis with scanning electron microscopy showed multidirectional fibers with diameters of 2–4.5 μm. The µF systems were hydrophobic and low cellular adhesion. The viability of CASMCs decreased with microfibers of 8% PCL and high CA concentration. However, the viability of CASMCs and HCAECs improved with 5% PCL and low CA concentration. Treatment with µF-TvE and µF-CA/TvE increased cell viability. HCAEC proliferation was affected by µF-CA, but incorporating TvE improved it. Platelet viability was unaffected by any µF system, but µF-CA and µF-CA/TvE inhibited the activation and adhesion of platelets. The results suggest that microfibers loaded with CA and TvE play a dual role in modifying HCAEC proliferation and blocking human platelet activation and adhesion. These findings have the potential to mitigate the atherosclerotic process. Full article

Patients with end-stage renal disease (ESRD) are at increased risk of cardiovascular disease (CVD), such as myocardial infarction (MI). Uremic toxins and endothelial dysfunction are central to this process. In this exploratory study, we used the Affymetrix GeneChip microarray to investigate the gene expression profile in uremic serum-induced human coronary arterial endothelial cells (HCAECs) from ESRD patients with and without MI (UWI and UWOI groups) as an approach to its underlying mechanism. We also explored which pathways are involved in this process. We found 100 differentially expressed genes (DEGs) among the conditions of interest by supervised principal component analysis and hierarchical cluster analysis. The expressions of four major DEGs were validated by quantitative RT-PCR. Pathway analysis and molecular network were used to analyze the interaction and expression patterns. Ten pathways were identified as the main enriched metabolic pathways according to the transcriptome profiling analysis, which were, among others, positive regulation of inflammatory response, positive regulation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) cascade, cardiac muscle cell development, highlighting positive regulation of mitogen-activated protein kinase (MAPK) activity (p = 0.00016). Up- and down-regulation of genes from HCAECs exposed to uremic serum could contribute to increased endothelial dysfunction and CVD in ESRD patients. Our study suggests that inflammation and the ERK-MAPK pathway are highly enriched in kidney disease patients with MI, suggesting their role in ESRD pathology. Further studies and approaches based on MAPK pathway interfering strategies are needed to confirm these data. Full article

Coronary artery spasm (CAS) is a reversible vasoconstriction of normal or atherosclerotic epicardial coronary arteries with a subsequent reduction in myocardial blood flow, leading to myocardial ischemia, myocardial infarction, severe arrhythmias, or even sudden death. It is an entity that should be recognized based on a particular clinical presentation. Numerous differences exist between CAS and obstructive coronary disease in terms of mechanisms, risk factors, and therapeutic solutions. The gold standard for CAS diagnosis is represented by transitory and reversible occlusion of the coronary arteries at spasm provocation test, which consists of an intracoronary administration of Ach, ergonovine, or methylergonovine during angiography. The pathophysiology of CAS is not fully understood. However, the core of CAS is represented by vascular smooth muscle cell contraction, with a circadian pattern. The initiating event of this contraction may be represented by endothelial dysfunction, inflammation, or autonomic nervous system unbalance. Our study explores the intricate balance of these factors and their clinical relevance in the management of CAS. Full article

Endothelial progenitor cells (EPCs) play a crucial role in vascular repair, and their depletion has been involved in coronary artery disease (CAD) severity. This study examines the relationship between circulating EPC levels and CAD complexity, as quantified by the Syntax Score I. A total of 85 patients undergoing coronary angiography were enrolled, with EPCs quantified using flow cytometry. EPC proportion showed a significant inverse relationship with CAD severity, measured by Syntax Score I. Additionally, we investigated EPC levels in patients presenting with acute coronary syndrome (ACS) and found that EPC depletion was more pronounced in this group compared to non-ACS patients (median EPC count: 0.35 vs. 0.61, p = 0.027). These findings suggest that lower EPC levels are indicative of more severe CAD and ACS, reinforcing their potential as biomarkers for cardiovascular risk stratification, monitoring disease advancement, and identifying patients at risk of adverse events. Full article

Oxidative stress plays a pivotal role in the pathogenesis of atherosclerosis and coronary artery disease (CAD), with both beneficial and detrimental effects on cardiovascular health. On one hand, the excessive production of reactive oxygen species (ROS) contributes to endothelial dysfunction, inflammation, and vascular remodeling, which are central to the development and progression of CAD. These pathological effects drive key processes such as atherosclerosis, plaque formation, and thrombosis. On the other hand, moderate levels of oxidative stress can have beneficial effects on cardiovascular health. These include regulating vascular tone by promoting blood vessel dilation, supporting endothelial function through nitric oxide production, and enhancing the immune response to prevent infections. Additionally, oxidative stress can stimulate cellular adaptation to stress, promote cell survival, and encourage angiogenesis, which helps form new blood vessels to improve blood flow. Oxidative stress also holds promise as a source of biomarkers that could aid in the diagnosis, prognosis, and monitoring of CAD. Specific oxidative markers, such as malondialdehyde (MDA), isoprostanes (isoP), ischemia-modified albumin, and antioxidant enzyme activity, have been identified as potential indicators of disease severity and therapeutic response. This review explores the dual nature of oxidative stress in atherosclerosis and CAD, examining its mechanisms in disease pathogenesis as well as its emerging role in clinical diagnostics and targeted therapies. The future directions for research aimed at harnessing the diagnostic and therapeutic potential of oxidative stress biomarkers are also discussed. Understanding the balance between the detrimental and beneficial effects of oxidative stress could lead to innovative approaches in the prevention and management of CAD. Full article

Coronary artery disease remains a leading cause of morbidity and mortality worldwide. Acute myocardial infarction results in ischemia-induced cellular dysfunction and death. While timely reperfusion limits myocardial damage, it paradoxically triggers ischemia–reperfusion injury (IRI), exacerbating tissue damage. IRI, first observed in the 1960s, is mediated by complex molecular pathways, including oxidative stress, calcium dysregulation, endothelial dysfunction, and inflammation. This review examines emerging therapeutic strategies targeting IRI, including ischemic preconditioning, postconditioning, pharmacological agents, and anti-inflammatory therapies. Preconditioning serves as an endogenous protection mechanism, while pharmacological postconditioning has become a more clinically feasible approach to target oxidative stress, inflammation, and apoptosis during reperfusion. Pharmacological agents, such as GSK-3β inhibitors, JNK inhibitors, and mesenchymal stem cell-derived exosomes, have shown promise in modulating molecular pathways, including Wnt/β-catenin and NF-κB, to reduce myocardial injury and enhance recovery. Combination therapies, integrating pharmacological agents with mechanical postconditioning, provide a synergistic approach to further protect tissue and mitigate damage. However, translating preclinical findings to clinical practice remains challenging due to discrepancies between animal models and human conditions, particularly with comorbidities such as diabetes and hypertension. Continued research is essential to refine these therapies, optimize clinical application, and address translational challenges to improve outcomes in IRI. Full article

Background: Vascular calcification (VC) is a characteristic feature of atherosclerosis in patients with chronic kidney disease (CKD), and coronary artery calcification (CAC) significantly impacts future cardiovascular events and mortality. Although factors associated with CAC are well reported, only a few studies have evaluated the factors associated with the progression of CAC in pre-dialysis patients with CKD. Methods: We quantitatively evaluated CAC progression using the CAC score (CACS) measured using 16-row multi-detector computed tomography and assessed associated factors in 74 patients with CKD. Results: The median annual increase in CACS was 23.7 (IQR 2.0–73.0). CAC progression was associated with serum phosphate and plasma asymmetric dimethylarginine (ADMA) levels, an endogenous inhibitor of nitric-oxide synthase and a marker of endothelial dysfunction and atherosclerosis, in univariate analysis. Multivariate analysis revealed that ADMA is an independent risk factor for CAC progression in patients with CKD. The annual change in CACS was significantly different between patients with ADMA values <0.51 and those with ADMA values >0.51 (p < 0.05). Elevated ADMA levels were also significantly associated with estimated glomerular filtration rate (eGFR) decline in the univariate analysis. Conclusions: ADMA is a novel risk factor for CAC progression in patients with CKD. Vascular endothelial cell dysfunction, represented by elevated ADMA levels, may contribute to the progression of vascular calcification in patients with pre-dialysis CKD. Full article

Acute and chronic coronary artery disease (CAD) are interconnected, representing two facets of the same condition. Chronic CAD exhibits a dynamic nature, manifesting as stable or acute ischemia, or both. Myocardial ischemia can be transient and reversible. The genesis of CAD involves diverse anatomical and functional mechanisms, including endothelial dysfunction, arteriolar remodeling, capillary rarefaction, and perivascular fibrosis, though no single factor explains its heterogeneity. Chronic CAD is often stable but may present as symptomatic or asymptomatic (e.g., in diabetes) and affect various coronary compartments (epicardial or microcirculation). This complexity necessitates a reappraisal of our approach, as pathophysiological mechanisms vary and often overlap. A comprehensive exploration of these mechanisms using advanced diagnostic techniques can aid in identifying the dynamic processes underlying CAD. The disease may present as obstructive or non-obstructive, stable or unstable, underscoring its diversity. The primary source of CAD lies in the arterial wall, emphasizing the need for research on its components, such as the endothelium and vascular smooth muscle cells, and factors disrupting arterial homeostasis. Shifting focus from arterial luminal status to the arterial wall can provide insights into the genesis of atheromatous plaques, enabling earlier interventions to prevent their development and progression. Full article

Despite significant advances in imaging modalities for diagnosing coronary artery disease (CAD), there remains a need for novel diagnostic approaches with high predictive values and fewer limitations. Circulating biomarkers, including cytokines such as interleukin-6 (IL-6) and interleukin-8 (IL-8), cell adhesion molecules such as soluble vascular cell adhesion molecule-1 (sVCAM-1), peptides secreted by endothelial cells such as endothelin-1 (ET-1), and enzymes involved in extracellular matrix remodeling such as a disintegrin and metalloproteinase with thrombospondin motifs-1 (ADAMTS-1) offer a promising alternative. This study aimed to evaluate the correlation between the plasma levels of selected biomarkers and the presence and severity of CAD. We enrolled 40 patients admitted for elective coronary angiography. CAD was defined as having at least one coronary artery stenosis ≥ 50%. The severity of CAD was assessed using the Gensini Score (GS). IL-8 levels were significantly higher in the CAD group, with a mean of 9.78 (SD 0.46) compared to 8.37 (SD 0.40) in the non-CAD group (p = 0.0228). No significant differences were observed for the other biomarkers between the groups. A positive Spearman correlation was found between IL-8 levels and the GS (ρ = 0.39, p = 0.017). These findings suggest that IL-8 may have potential as an additional tool for diagnosing or excluding atherosclerosis. Further studies with larger sample sizes are needed to validate its clinical utility. Full article