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Indian Heart Journal Mar 2024Lp(a) is a genetically determined, heritable, independent and causal risk factor for ASCVD. About 1 in 5 people worldwide have elevated Lp(a) (>50 mg/dL or... (Review)
Review
Lp(a) is a genetically determined, heritable, independent and causal risk factor for ASCVD. About 1 in 5 people worldwide have elevated Lp(a) (>50 mg/dL or >125 nmol/L) whereas in Indians it is 25 %. Epidemiological, genome-wide association and mendelian randomization studies have demonstrated an association between elevated Lp(a) levels and increased incidence of myocardial infarction, aortic valve stenosis, ischemic stroke, heart failure, CV and all-cause mortality. The increased Lp(a)-mediated CV risk is mediated by pro-inflammatory, pro-thrombotic and pro-atherogenic processes, leading to progression of atherosclerosis and increased risk of thrombosis. Lp(a) level reaches peak by 5 years of age and remains stable over time. Levels are not much influenced by dietary and environmental factors but it can vary in certain clinical situations like thyroid diseases, chronic kidney disease, inflammation and sepsis. It should be measured at least once in life time. Cascade testing for high Lp(a) is recommended in the settings of FH, family history of (very) high Lp(a), and personal or family history of ASCVD. In the absence of specific Lp(a)-lowering therapies, comprehensive risk factor management is recommended as per guidelines for individuals with elevated Lp(a). PCSK9 inhibitors and Inclisiran reduce Lp(a) by 25%. Pelacarsen is an antisense oligonucleotide and is found to reduce Lp(a) by 80%. In a recent Indian study of 1,021 CAD patients, presence of elevated Lp(a) (>50 mg/dL) correlated with severe angiographic disease. 37% of ACS patients exhibited elevated Lp(a) and it was higher in young CAD patients with FH (43%).
Topics: Humans; Proprotein Convertase 9; Lipoprotein(a); Genome-Wide Association Study; Risk Factors; Atherosclerosis; Hyperlipidemias
PubMed: 38160790
DOI: 10.1016/j.ihj.2023.12.010 -
Chinese Medical Journal Oct 2015This review aimed to summarize the relationship between intestinal microbiota metabolism and cardiovascular disease (CVD) and to propose a novel CVD therapeutic target. (Review)
Review
OBJECTIVE
This review aimed to summarize the relationship between intestinal microbiota metabolism and cardiovascular disease (CVD) and to propose a novel CVD therapeutic target.
DATA SOURCES
This study was based on data obtained from PubMed and EMBASE up to June 30, 2015. Articles were selected using the following search terms: "Intestinal microbiota", "trimethylamine N-oxide (TMAO)", "trimethylamine (TMA)", "cardiovascular", and "atherosclerosis".
STUDY SELECTION
Studies were eligible if they present information on intestinal microbiota metabolism and atherosclerosis. Studies on TMA-containing nutrients were also included.
RESULTS
A new CVD risk factor, TMAO, was recently identified. It has been observed that several TMA-containing compounds may be catabolized by specific intestinal microbiota, resulting in TMA release. TMA is subsequently converted to TMAO in the liver. Several preliminary studies have linked TMAO to CVD, particularly atherosclerosis; however, the details of this relationship remain unclear.
CONCLUSIONS
Intestinal microbiota metabolism is associated with atherosclerosis and may represent a promising therapeutic target with respect to CVD management.
Topics: Atherosclerosis; Gastrointestinal Microbiome; Humans; Methylamines
PubMed: 26481750
DOI: 10.4103/0366-6999.167362 -
Current Atherosclerosis Reports May 2016Historically, the relationship between exercise and the cardiovascular system was viewed as unidirectional, with a disease resulting in exercise limitation and hazard.... (Review)
Review
Historically, the relationship between exercise and the cardiovascular system was viewed as unidirectional, with a disease resulting in exercise limitation and hazard. This article reviews and explores the bidirectional nature, delineating the effects, generally positive, on the cardiovascular system and atherosclerosis. Exercise augments eNOS, affects redox potential, and favorably affects mediators of atherosclerosis including lipids, glucose homeostasis, and inflammation. There are direct effects on the vasculature as well as indirect benefits related to exercise-induced changes in body composition and skeletal muscle. Application of aerobic exercise to specific populations is described, with the hope that this knowledge will move the science forward and improve individual patient outcome.
Topics: Atherosclerosis; Body Composition; Cardiovascular Diseases; Cardiovascular System; Exercise; Humans; Physical Fitness
PubMed: 27005804
DOI: 10.1007/s11883-016-0580-7 -
Nutrients Aug 2020Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality worldwide [...].
Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality worldwide [...].
Topics: Atherosclerosis; Cholesterol; Diabetes Mellitus, Type 2; Diet, Mediterranean; Humans; Inflammation; Life Style; Nutritional Physiological Phenomena; Obesity
PubMed: 32823869
DOI: 10.3390/nu12082444 -
Journal of the American College of... Dec 2014Atherosclerosis is an immune-mediated inflammatory disease of the arterial wall, with both the innate and adaptive immune systems responding to many endogenous and... (Review)
Review
Atherosclerosis is an immune-mediated inflammatory disease of the arterial wall, with both the innate and adaptive immune systems responding to many endogenous and exogenous antigens. Both proatherogenic as well as atheroprotective roles have been identified for the immune system in atherosclerosis. Hence, it is conceivable that an immunomodulatory strategy via active immunization against many of these antigens could potentially alter the natural history of atherosclerosis. This review discusses: 1) the complex role of important components of the innate and adaptive immune systems in atherogenesis; 2) the nature of many antigens that have been tested successfully in vaccine formulations to reduce atherosclerosis in pre-clinical experimental models; and 3) the potential opportunities and challenges for clinical application of vaccination for atherosclerosis in the future.
Topics: Adaptive Immunity; Atherosclerosis; Humans; Immunity, Innate; Vaccines
PubMed: 25541132
DOI: 10.1016/j.jacc.2014.10.018 -
Advanced Drug Delivery Reviews Mar 2021Atherosclerosis is a chronic inflammatory disease driven by lipid accumulation in arteries, leading to narrowing and thrombosis. It affects the heart, brain, and... (Review)
Review
Atherosclerosis is a chronic inflammatory disease driven by lipid accumulation in arteries, leading to narrowing and thrombosis. It affects the heart, brain, and peripheral vessels and is the leading cause of mortality in the United States. Researchers have strived to design nanomaterials of various functions, ranging from non-invasive imaging contrast agents, targeted therapeutic delivery systems to multifunctional nanoagents able to target, diagnose, and treat atherosclerosis. Therefore, this review aims to summarize recent progress (2017-now) in the development of nanomaterials and their applications to improve atherosclerosis diagnosis and therapy during the preclinical and clinical stages of the disease.
Topics: Animals; Atherosclerosis; Humans; Nanostructures
PubMed: 33428994
DOI: 10.1016/j.addr.2021.01.005 -
Current Atherosclerosis Reports Nov 2017The cell surface-attached extracellular glycocalyx (GCX) layer is a major contributor to endothelial cell (EC) function and EC-dependent vascular health and is a first... (Review)
Review
PURPOSE OF REVIEW
The cell surface-attached extracellular glycocalyx (GCX) layer is a major contributor to endothelial cell (EC) function and EC-dependent vascular health and is a first line of defense against vascular diseases including atherosclerosis. Here, we highlight our findings regarding three GCX-dependent EC functions, which are altered when GCX is shed and in atherosclerosis. We discuss why the GCX is a viable option for the prevention and treatment of atherosclerosis.
RECENT FINDINGS
GCX regulated EC activities such as barrier and filtration function, active cell-to-cell communication, and vascular tone mediation contribute to function of the entire vascular wall. Atheroprone vessel regions, including bifurcation sites, exhibit breakdown in GCX. This GCX degradation allows increased lipid flux and thereby promotes lipid deposition in the vessel walls, a hallmark of atherosclerosis. GCX degradation also alters EC-to-EC communication while increasing EC-to-inflammatory cell interactions that enable inflammatory cells to migrate into the vessel wall. Inflammatory macrophages and foam cells, to be specific, appear in early stages of atherosclerosis. Furthermore, GCX degradation deregulates vascular tone, by causing ECs to reduce their expression of endothelial nitric oxide synthase (eNOS) which produces the vasodilator, nitric oxide. Loss of vasodilation supports vasoconstriction, which promotes the progression of atherosclerosis. Common medicinal atherosclerosis therapies include lipid lowering and anti-platelet therapies. None of these treatments specifically target the endothelial GCX, although the GCX is at the front-line in atherosclerosis combat. This review demonstrates the viability of targeting the GCX therapeutically, to support proper EC functionality and prevent and/or treat atherosclerosis.
Topics: Animals; Atherosclerosis; Endothelial Cells; Endothelium, Vascular; Glycocalyx; Humans; Models, Animal; Molecular Targeted Therapy
PubMed: 29127504
DOI: 10.1007/s11883-017-0691-9 -
Current Cardiology Reviews 2020The article provides an overview of current views on the role of biomechanical forces in the pathogenesis of atherosclerosis. The importance of biomechanical forces in... (Review)
Review
The article provides an overview of current views on the role of biomechanical forces in the pathogenesis of atherosclerosis. The importance of biomechanical forces in maintaining vascular homeostasis is considered. We provide descriptions of mechanosensing and mechanotransduction. The roles of wall shear stress and circumferential wall stress in the initiation, progression and destabilization of atherosclerotic plaque are described. The data on the possibilities of assessing biomechanical factors in clinical practice and the clinical significance of this approach are presented. The article concludes with a discussion on current therapeutic approaches based on the modulation of biomechanical forces.
Topics: Atherosclerosis; Biomechanical Phenomena; Disease Progression; Humans; Mechanotransduction, Cellular; Stress, Mechanical
PubMed: 31362692
DOI: 10.2174/1573403X15666190730095153 -
Current Opinion in Lipidology Aug 2018We provide an overview of recent publications that extend clinically relevant knowledge relating to metformin's effects on lipids and atherosclerotic vascular disease... (Review)
Review
PURPOSE OF REVIEW
We provide an overview of recent publications that extend clinically relevant knowledge relating to metformin's effects on lipids and atherosclerotic vascular disease and/or provide insights into the drug's mechanisms of action on the heart and vasculature.
RECENT FINDINGS
We focus on original research in humans or in human tissues. Several recently completed randomized clinical trials have reported effects of metformin on surrogate measures of atherosclerotic vascular disease, including carotid-intima media thickness, vascular reactivity and calcification in people with Type 1 (T1D) and Type 2 (T2D) diabetes as well as nondiabetic dysglycaemia. In addition, observational studies have provided novel insights into the mechanisms of metformin's effects on carotid plaque, monocytes/macrophages, vascular smooth muscle and endothelial cells, including via 5'-adenosine monophosphate-activated protein kinase (AMPK) activation.
SUMMARY
Recent trials based on surrogate outcome measures have provided further data suggesting protective effects of metformin against vascular disease in youth and adults with Type 1 diabetes, as well as in adults with prediabetes and Type 2 diabetes. In parallel, human tissue and cell studies have provided new insights into pleiotropic effects of metformin and suggest novel drug targets. As metformin is an inexpensive agent with an established safety profile, larger scale clinical trials based on hard clinical outcomes [cardiovascular disease (CVD) events] are now indicated.
Topics: Atherosclerosis; Blood Vessels; Humans; Lipid Metabolism; Metformin
PubMed: 29878903
DOI: 10.1097/MOL.0000000000000532 -
Cell Communication and Signaling : CCS Nov 2023Atherosclerosis, which is a vascular pathology characterized by inflammation and plaque build-up within arterial vessel walls, acts as the important cause of most... (Review)
Review
Atherosclerosis, which is a vascular pathology characterized by inflammation and plaque build-up within arterial vessel walls, acts as the important cause of most cardiovascular diseases. Except for a lipid-depository and chronic inflammatory, increasing evidences propose that epigenetic modifications are increasingly associated with atherosclerosis and are of interest from both therapeutic and biomarker perspectives. The chronic progressive nature of atherosclerosis has highlighted atherosclerosis heterogeneity and the fact that specific cell types in the complex milieu of the plaque are, by far, not the only initiators and drivers of atherosclerosis. Instead, the ubiquitous effects of cell type are tightly controlled and directed by the epigenetic signature, which, in turn, is affected by many proatherogenic stimuli, including low-density lipoprotein, proinflammatory, and physical forces of blood circulation. In this review, we summarize the role of DNA methylation and histone post-translational modifications in atherosclerosis. The future research directions and potential therapy for the management of atherosclerosis are also discussed. Video Abstract.
Topics: Humans; DNA Methylation; Histones; Atherosclerosis; Plaque, Atherosclerotic; Epigenesis, Genetic; Protein Processing, Post-Translational; Inflammation
PubMed: 38031118
DOI: 10.1186/s12964-023-01298-8