Search Results (4,464)

Non-vitamin K oral anticoagulants (NOACs) have revolutionized anticoagulant therapy, offering improved safety and efficacy over traditional agents like warfarin. This review comprehensively examines the dual roles of NOACs—apixaban, rivaroxaban, edoxaban, and dabigatran—not only as anticoagulants, but also as modulators of inflammation via protease-activated receptor (PAR) signaling. We highlight the unique pharmacotherapeutic properties of each NOAC, supported by key clinical trials demonstrating their effectiveness in preventing thromboembolic events. Beyond their established anticoagulant roles, emerging research suggests that NOACs influence inflammation through PAR signaling pathways, implicating factors such as factor Xa (FXa) and thrombin in the modulation of inflammatory responses. This review synthesizes current evidence on the anti-inflammatory potential of NOACs, exploring their impact on inflammatory markers and conditions like atherosclerosis and diabetes. By delineating the mechanisms by which NOACs mediate anti-inflammatory effects, this work aims to expand their therapeutic utility, offering new perspectives for managing inflammatory diseases. Our findings underscore the broader clinical implications of NOACs, advocating for their consideration in therapeutic strategies aimed at addressing inflammation-related pathologies. This comprehensive synthesis not only enhances understanding of NOACs’ multifaceted roles, but also paves the way for future research and clinical applications in inflammation and cardiovascular health. Full article

Laminins are essential components of the basement membranes, expressed in a tissue- and cell-specific manner under physiological conditions. During inflammatory circumstances, such as atherosclerosis, alterations in laminin composition within vessels have been observed. Our study aimed to assess the influence of tumor necrosis factor-alpha (TNF), a proinflammatory cytokine abundantly found in atherosclerotic lesions, on endothelial laminin gene expression and the effects of laminin-332 (LN332) on endothelial cells’ behavior. We also evaluated the expression of LN332-encoding genes in human carotid atherosclerotic plaques. Our findings demonstrate that TNF induces upregulation of LAMB3 and LAMC2, which, along with LAMA3, encode the LN332 isoform. Endothelial cells cultured on recombinant LN332 exhibit decreased claudin-5 expression and display a loosely connected phenotype, with an elevated expression of chemokines and leukocyte adhesion molecules, enhancing their attractiveness and adhesion to leukocytes in vitro. Furthermore, LAMB3 and LAMC2 are upregulated in human carotid plaques and show a positive correlation with TNF expression. In summary, TNF stimulates the expression of LN332-encoding genes in human endothelial cells and LN332 promotes an endothelial phenotype characterized by compromised junctional integrity and increased leukocyte interaction. These findings highlight the importance of basement membrane proteins for endothelial integrity and the potential role of LN332 in atherosclerosis. Full article

Owing to their potent glucose-lowering efficacy and substantial weight loss effects, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are now considered part of the frontline therapeutic options to treat both type 2 diabetes mellitus and nondiabetic overweight/obesity. Stemming from successful demonstration of their cardiometabolic modulation and reduction of major adverse cardiovascular events in clinical outcome trials, GLP-1 RAs have since been validated as agents with compelling cardiovascular protective properties. Studies spanning from the bench to preclinical and large-scale randomised controlled trials have consistently corroborated the cardiovascular benefits of this pharmacological class. Most notably, there is converging evidence that they exert favourable effects on atherosclerotic ischaemic endpoints, with preclinical data indicating that they may do so by directly modifying the burden and composition of atherosclerotic plaques. This narrative review examines the underlying pharmacology and clinical evidence behind the cardiovascular benefits of GLP-1 RAs, with particular focus on atherosclerotic cardiovascular disease. It also delves into the mechanisms that underpin their putative plaque-modifying actions, addresses existing knowledge gaps and therapeutic challenges and looks to future developments in the field, including the use of combination incretin agents for diabetes and weight loss management. Full article

The COVID-19 pandemic has raised awareness of the virus’s long-term non-pulmonary consequences. This study examined the relationship between genetic polymorphisms of VEGF and cardiac dysfunction and subclinical atherosclerosis in patients recovering from COVID-19. This study included 67 patients previously diagnosed with COVID-19. VEGF-936C/T, VEGF-634G/C, and VEGF-2578C/A statuses were determined. Conventional echocardiography and arterial parameters assessments were performed at inclusion and at six months after the first assessment. For VEGF-936C/T, dominant and over-dominant models showed a significant increase in ejection fraction at six months after COVID (p = 0.044 and 0.048) and was also a predictive independent factor for the augmentation index (β = 3.07; p = 0.024). The dominant model showed a rise in RV-RA gradient (3.702 mmHg) (p = 0.028 95% CI: 0.040–7.363), with the over-dominant model indicating a greater difference (4.254 mmHg) (p = 0.025 95% CI: 0.624–7.884). The findings for VEGF-634G/C were not statistically significant, except for a difference in TAPSE during initial evaluation, using the codominant model. For VEGF-2578C/A, a difference in ventricular filling pressure (E/E’ratio) was best described under the recessive model. Our research suggests that the VEG-936C/T genotype may impact the baseline level and subsequent changes in cardiac function and subclinical atherosclerosis. These findings offer valuable insights into the complex correlation between genetic polymorphisms and cardiovascular disfunction in long COVID patients. Full article

Background: Recently, the arterial velocity pulse index (AVI) and arterial pressure volume index (API) have been used to evaluate arterial stiffness and endothelial function. As arterial stiffness and endothelial injury are risk factors for coronary artery disease (CAD), these two indexes are therefore expected to predict and evaluate the future risk of CAD and cardiovascular events before clinical manifestations. Methods: A total of 90 consecutive patients with coronary angiography (CAG) were enrolled. After excluding normal patients and acute coronary syndrome patients, forty-seven patients with CAD and thirty-two patients with coronary atherosclerosis, and baseline characteristics data were collected. A multifunctional blood pressure monitoring device, AVE-1500 (Shisei Datum, Tokyo, Japan), was used to measure the AVI and API before CAG, and immediately and 2 h, 24 h, and 48 h after CAG and (or) PCI in all the selected participants. Results: After adjusting for various variables using stepwise multiple linear regression analyses, we found that the AVI in the CAD subjects was significantly higher than that in the coronary atherosclerosis subjects before CAG (p = 0.02), immediately after CAG/PCI (p = 0.01), and 48 h after CAG/PCI (p = 0.01), whereas the AVI decreased 24–48 h rather than immediately after CAG/PCI in the CAD group. Moreover, we also found that the API clearly changed in both groups during the periprocedural period of CAG (p = 0.01). Conclusions: In accordance with the results, we propose that the API and AVI may be useful for predicting the early stage of CAD and may be promising as indicators to assess the effect of early revascularization. Full article

As a critical part of the circulatory system, blood vessels transport oxygen and nutrients to every corner of the body, nourishing each cell, and also remove waste and toxins. Defects in vascular development and function are closely associated with many diseases, such as heart disease, stroke, and atherosclerosis. In the nervous system, the nervous and vascular systems are intricately connected in both development and function. First, peripheral blood vessels and nerves exhibit parallel distribution patterns. In the central nervous system (CNS), nerves and blood vessels form a complex interface known as the neurovascular unit. Second, the vascular system employs similar cellular and molecular mechanisms as the nervous system for its development. Third, the development and function of CNS vasculature are tightly regulated by CNS-specific signaling pathways and neural activity. Additionally, vascular endothelial cells within the CNS are tightly connected and interact with pericytes, astrocytes, neurons, and microglia to form the blood–brain barrier (BBB). The BBB strictly controls material exchanges between the blood and brain, maintaining the brain’s microenvironmental homeostasis, which is crucial for the normal development and function of the CNS. Here, we comprehensively summarize research on neural regulation of vascular and BBB development and propose directions for future research. Full article

Poor diet is the top modifiable mortality risk factor globally, accounting for 11 million deaths annually with half being from diet-linked atherosclerotic cardiovascular disease (ASCVD). Yet, most of the world cannot afford a healthy diet—as the hidden costs of the inadequate global food system total over USD 13 trillion annually—let alone the much more clinically, financially, and ecologically costly and resource-intensive medical interventions required to address the disease progression and acute complications of ASCVD. Yet, AI is increasingly understood as a force multiplying revolutionary technology which may catalyze multi-sector efforts in medicine and public health to better address these significant health challenges. This novel narrative review seeks to provide the first known overview of the state-of-the-art in clinical interventions and public health policies in healthy diets for ASCVD, accelerated by health equity-focused AI. It is written from the first-hand practitioner perspective to provide greater relevance and applicability for health professionals and data scientists. The review summarizes the emerging trends and leading use cases in population health risk stratification and precision public health, AI democratizing clinical diagnosis, digital twins in precision nutrition, and AI-enabled culinary medicine as medical education and treatment. This review may, therefore, help inform and advance the evidence-based foundation for more clinically effective, financially efficient, and societally equitable dietary and nutrition interventions for ASCVD. Full article

Traditionally focused on obstructive atherosclerosis, contemporary research indicates that up to 70% of patients undergoing coronary angiography for angina and ischemic symptoms do not exhibit significant stenoses. Nonobstructive coronary artery disease (CAD) has emerged as a prevalent phenotype among these patients. This review emphasizes the emerging understanding that nonobstructive coronary artery disease, encompassing conditions such as ANOCA (Angina with No Obstructive Coronary Artery Disease), INOCA (Ischemia with No Obstructive Coronary Artery Disease), and MINOCA (Myocardial Infarction with No Obstructive Coronary Arteries), represents the most prevalent phenotype in cardiac patients. It delves into the complex pathophysiology underlying these conditions, focusing on microvascular dysfunction and coronary vasoreactivity, which contribute to myocardial ischemia despite the absence of significant coronary obstructions. Additionally, the review critically examines the limitations of current treatments which primarily target obstructive lesions and underscores the necessity for tailored therapies that address the specific microvascular and immunoinflammatory pathways involved in nonobstructive CAD. The main focus of this review is to advocate for a shift in diagnostic and therapeutic strategies to better identify and manage this widely prevalent yet under-recognized subset of CAD. Full article

Cardiac mesoderm enhancer-associated non-coding RNA (CARMN), an evolutionarily conserved long non-coding RNA (lncRNA), serves as the host gene for the miR143/145 cluster. It plays a crucial role in cardiovascular cell differentiation and the maintenance of vascular smooth muscle cell (VSMC) homeostasis, which are vital for normal physiological processes. Specifically, CARMN is associated with the pathological progression of cardiovascular diseases such as atherosclerosis, abdominal aortic aneurysm, and chronic heart failure. Moreover, it acts as a tumor suppressor in various cancers, including hepatocellular carcinoma, bladder cancer, and breast cancer, highlighting its potential as a beneficial biomarker and therapeutic target. This review provides a detailed examination of the roles of CARMN, its evolutionary conservation, expression patterns, and regulatory mechanisms. It also outlines its significant implications in the diagnosis, prognosis, and treatment of these diseases, underscoring the need for further translational research to exploit its clinical potential. Full article

Calcification refers to the deposition of calcium-containing crystals either intracellularly or within the extracellular matrix. Physiologic calcification is a normal process occurring during bone and tooth development and growth. In contrast, pathologic calcification occurs in soft tissues that typically do not undergo mineralization, such as blood vessels, cartilage, tendons, and skin. Pathological calcification is significantly associated with tissue impairment and the development of secondary diseases, such as atherosclerosis, osteoarthritis, tendinopathy, and skin ulcers. Aging, a natural process linked to numerous pathologic conditions, is one of the most recognized risk factors for pathological calcification. In this manuscript, we review the current state of knowledge regarding the role of aging in calcification across different tissues. We focus on the mechanisms activated during normal aging, including cellular senescence, decreased pyrophosphate levels, increased secretion of extracellular vesicles, elevated oxidative stress, and higher levels of pro-mineralizing cytokines, all of which can contribute to pathological calcification. Finally, we discuss the available animal models used to study the impact of aging on calcification. Full article

Antioxidants are endogenous and exogenous substances with the ability to inhibit oxidation processes by interacting with reactive oxygen species (ROS). ROS, in turn, are small, highly reactive substances capable of oxidizing a wide range of molecules in the human body, including nucleic acids, proteins, lipids, carbohydrates, and even small inorganic compounds. The overproduction of ROS leads to oxidative stress, which constitutes a significant factor contributing to the development of disease, not only markedly diminishing the quality of life but also representing the most common cause of death in developed countries, namely, cardiovascular disease (CVD). The aim of this review is to demonstrate the effect of selected antioxidants, such as coenzyme Q10 (CoQ10), flavonoids, carotenoids, and resveratrol, as well as to introduce new antioxidant therapies utilizing miRNA and nanoparticles, in reducing the incidence and progression of CVD. In addition, new antioxidant therapies in the context of the aforementioned diseases will be considered. This review emphasizes the pleiotropic effects and benefits stemming from the presence of the mentioned substances in the organism, leading to an overall reduction in cardiovascular risk, including coronary heart disease, dyslipidaemia, hypertension, atherosclerosis, and myocardial hypertrophy. Full article

Inflammation is the body’s non-specific response to injury or infection. It is a natural defense mechanism that helps to maintain homeostasis and promotes tissue repair. However, excessive inflammation can lead to cellular, tissue, or organ dysfunction, as well as contribute to the development of acute vascular events and diseases like Crohn’s disease, psoriasis, obesity, diabetes, and cancer. The initial response to injury involves the activation of platelets and coagulation mechanisms to stop bleeding. This is followed by the recruitment of immune cells and the release of cytokines to promote tissue repair. Over time, the injured tissue undergoes remodeling and returns to its pre-injury state. Inflammation is characterized by the activation of inflammatory signaling pathways involving cytokines, chemokines, and growth factors. Mast cells play a role in initiating inflammatory responses. Pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and nucleotide-binding domain (NOD)-like receptors (NLRs) are involved in the activation of these inflammatory pathways. Inflammasomes, which are cytoplasmic complexes, also contribute to inflammation by activating cytokines. Inflammation can also be triggered by factors like dietary components and the composition of the gut microbiota. Dysregulation of the gut microbiome can lead to excessive inflammation and contribute to diseases like atherosclerosis and irritable bowel syndrome (IBS). The immune system and gut-associated lymphoid tissue (GALT) play crucial roles in the inflammatory response and the development of conditions like colorectal cancer. Anti-inflammatory therapy can play a significant role in reducing or inducing the remission of inflammatory diseases such as Crohn’s disease and ulcerative colitis. The fetal origin of adult diseases theory suggests that conditions during fetal development, such as low birth weight and maternal obesity, can influence the risk of cardiometabolic diseases later in life. All of the known risk factors associated with cardiometabolic diseases such as hypertension, excess weight, obesity, type-2 diabetes, and vascular diseases are accompanied by chronic low-grade inflammation. Inflammation seems to have a role in precipitating even acute vascular events such as heart attacks and stroke. Common markers of inflammation associated with cardiometabolic disease include interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF-α), C-reactive protein (CRP), and soluble TNF receptors such as sTNFR1 and sTNFR2. These markers serve as indicators of systemic inflammation. However, these markers are not disease-specific but provide an insight into the overall chronic inflammatory status. In fact, inflammation has been identified as a potential target for future treatments to reduce or reverse the risk of atherosclerosis-related complications. The regulation of inflammation is complex, and further research is needed to better understand its mechanisms and develop strategies for managing inflammatory disorders. In summary, inflammation is a natural response to injury or infection, but excessive or prolonged inflammation can lead to the progression of various diseases. Understanding the underlying mechanisms of inflammation is important for developing treatments and preventive measures for inflammatory disorders. Full article

Conjugated linoleic acid (CLA) is a class of bioactive fatty acids that exhibit various physiological activities such as anti-cancer, anti-atherosclerosis, and lipid-lowering. It is an essential fatty acid that cannot be synthesized by the human body and must be derived from dietary sources. The natural sources of CLA are limited, predominantly relying on chemical and enzymatic syntheses methods. Microbial biosynthesis represents an environmentally benign approach for CLA production. Pine nut oil, containing 40–60% linoleic acid, serves as a promising substrate for CLA enrichment. In the present study, we developed a novel method for the production of CLA from pine nut oil using Lactiplantibacillus plantarum (L. plantarum) Lp-01, which harbors a linoleic acid isomerase. The optimal fermentation parameters for CLA production were determined using a combination of single-factor and response surface methodologies: an inoculum size of 2%, a fermentation temperature of 36 °C, a fermentation time of 20 h, and a pine nut oil concentration of 11%. Under these optimized conditions, the resultant CLA yield was 33.47 μg/mL. Gas chromatography analysis revealed that the fermentation process yielded a mixture of c9, t11CLA and t10, c12 CLA isomers, representing 4.91% and 4.86% of the total fatty acid content, respectively. Full article

Atherosclerosis, marked by plaque accumulation within arteries, results from lipid dysregulation, inflammation, and vascular remodeling. Plaque composition, including lipid-rich cores and fibrous caps, determines stability and vulnerability. Photodynamic therapy (PDT) has emerged as a promising treatment, leveraging photosensitizers to induce localized cytotoxicity upon light activation. PDT targets plaque components selectively, reducing burden and inflammation. Challenges remain in optimizing PDT parameters and translating preclinical success to clinical efficacy. Nonetheless, PDT offers a minimally invasive strategy for atherosclerosis management, promising personalized interventions for cardiovascular health. The objective of the current study was to present the findings from quantitative non-contrast MRI of atherosclerosis post-PDT by assessing relaxation times. The study aimed to utilize and optimize a 1.5T MRI system. Clinical scanners were used for MRI examinations. The research involved analyzing T1 and T2 relaxation times. Following treatment of the samples with Rose Bengal and exposure to pure oxygen, PDT irradiation was administered. The results indicated that the therapy impacted the crus, evidenced by a significant decrease in relaxation times in the MRI data. Full article

We aimed to characterize the anti-obesity and anti-atherosclerosis effects of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 using high-fat diet (HFD)-fed obese C57BL/6 mice. We divided the mice into control (CON), HFD, HFD with 10⁸ CFU/kg/day probiotics (HFD + KL, HY7301:KY1032 = 1:1), and HFD with 10⁹ CFU/kg/day probiotics (HFD + KH, HY7301:KY1032 = 1:1) groups and fed/treated them during 7 weeks. The body mass, brown adipose tissue (BAT), inguinal white adipose tissue (iWAT), and epididymal white adipose tissue (eWAT) masses and the total cholesterol and triglyceride concentrations were remarkably lower in probiotic-treated groups than in the HFD group in a dose-dependent manner. In addition, the expression of uncoupling protein 1 in the BAT, iWAT, and eWAT was significantly higher in probiotic-treated HFD mice than in the HFD mice, as demonstrated by immunofluorescence staining and Western blotting. We also measured the expression of cholesterol transport genes in the liver and jejunum and found that the expression of those encoding liver-X-receptor α, ATP-binding cassette transporters G5 and G8, and cholesterol 7α-hydroxylase were significantly higher in the HFD + KH mice than in the HFD mice. Thus, a Lactobacillus HY7601 and KY1032 mixture with 10⁹ CFU/kg/day concentration can assist with body weight regulation through the management of lipid metabolism and thermogenesis. Full article