0
selected
-
1.
Immune Checkpoint Therapies and Atherosclerosis: Mechanisms and Clinical Implications: JACC State-of-the-Art Review.
Vuong, JT, Stein-Merlob, AF, Nayeri, A, Sallam, T, Neilan, TG, Yang, EH
Journal of the American College of Cardiology. 2022;(6):577-593
Abstract
Immune checkpoint inhibitor therapy has revolutionized the treatment of advanced malignancies in recent years. Numerous reports have detailed the myriad of possible adverse inflammatory effects of immune checkpoint therapies, including within the cardiovascular system. However, these reports have been largely limited to myocarditis. The critical role of inflammation and adaptive immunity in atherosclerosis has been well characterized in preclinical studies, and several emerging clinical studies indicate a potential role of immune checkpoint targeting therapies in the development and exacerbation of atherosclerosis. In this review, we provide an overview of the role of T-cell immunity in atherogenesis and describe the molecular effects and clinical associations of both approved and investigational immune checkpoint therapy on atherosclerosis. We also highlight the role of cholesterol metabolism in oncogenesis and discuss the implications of these associations on future treatment and monitoring of atherosclerotic cardiovascular disease in the oncologic population receiving immune checkpoint therapy.
-
2.
Leukocyte Trafficking via Lymphatic Vessels in Atherosclerosis.
Yeo, KP, Lim, HY, Angeli, V
Cells. 2021;(6)
Abstract
In recent years, lymphatic vessels have received increasing attention and our understanding of their development and functional roles in health and diseases has greatly improved. It has become clear that lymphatic vessels are critically involved in acute and chronic inflammation and its resolution by supporting the transport of immune cells, fluid, and macromolecules. As we will discuss in this review, the involvement of lymphatic vessels has been uncovered in atherosclerosis, a chronic inflammatory disease of medium- and large-sized arteries causing deadly cardiovascular complications worldwide. The progression of atherosclerosis is associated with morphological and functional alterations in lymphatic vessels draining the diseased artery. These defects in the lymphatic vasculature impact the inflammatory response in atherosclerosis by affecting immune cell trafficking, lymphoid neogenesis, and clearance of macromolecules in the arterial wall. Based on these new findings, we propose that targeting lymphatic function could be considered in conjunction with existing drugs as a treatment option for atherosclerosis.
-
3.
Role of Telomeres Shortening in Atherogenesis: An Overview.
Yegorov, YE, Poznyak, AV, Nikiforov, NG, Starodubova, AV, Orekhov, AN
Cells. 2021;(2)
Abstract
It is known that the shortening of the telomeres leads to cell senescence, accompanied by acquiring of pro-inflammatory phenotype. The expression of telomerase can elongate telomeres and resist the onset of senescence. The initiation of atherosclerosis is believed to be associated with local senescence of the endothelial cells of the arteries in places with either low or multidirectional oscillatory wall shear stress. The process of regeneration of the artery surface that has begun does not lead to success for several reasons. Atherosclerotic plaques are formed, which, when developed, lead to fatal consequences, which are the leading causes of death in the modern world. The pronounced age dependence of the manifestations of atherosclerosis pushes scientists to try to link the development of atherosclerosis with telomere length. The study of the role of telomere shortening in atherosclerosis is mainly limited to measuring the telomeres of blood cells, and only in rare cases (surgery or post-mortem examination) are the telomeres of local cells available for measurement. The review discusses the basic issues of cellular aging and the interpretation of telomere measurement data in atherosclerosis, as well as the prospects for the prevention and possible treatment of atherosclerosis.
-
4.
Sex-Related Differences in Cardiovascular Disease Risk Profile in Children and Adolescents with Type 1 Diabetes.
Smigoc Schweiger, D, Battelino, T, Groselj, U
International journal of molecular sciences. 2021;(19)
Abstract
Cardiovascular disease (CVD) is the primary cause of higher and earlier morbidity and mortality in people with type 1 diabetes (T1D) compared to people without diabetes. In addition, women with T1D are at an even higher relative risk for CVD than men. However, the underlying pathophysiology is not well understood. Atherosclerotic changes are known to progress early in life among people with T1D, yet it is less clear when excess CVD risk begins in females with T1D. This review explores the prevalence of classical CVD risk factors (such as glycemic control, hypertension, dyslipidemia, obesity, albuminuria, smoking, diet, physical inactivity), as well as of novel biomarkers (such as chronic inflammation), in children and adolescents with T1D with particular regard to sex-related differences in risk profile. We also summarize gaps where further research and clearer clinical guidance are needed to better address this issue. Considering that girls with T1D might have a more adverse CVD risk profile than boys, the early identification of and sex-specific intervention in T1D would have the potential to reduce later CVD morbidity and excess mortality in females with T1D. To conclude, based on an extensive review of the existing literature, we found a clear difference between boys and girls with T1D in the presence of individual CVD risk factors as well as in overall CVD risk profiles; the girls were on the whole more impacted.
-
5.
PCSK9 and atherosclerosis: Looking beyond LDL regulation.
Ragusa, R, Basta, G, Neglia, D, De Caterina, R, Del Turco, S, Caselli, C
European journal of clinical investigation. 2021;(4):e13459
Abstract
Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) is involved in cholesterol homeostasis. After binding to the complex low-density lipoprotein (LDL)-receptor, PCSK9 induces its intracellular degradation, thus reducing serum LDL clearance. In addition to the well-known activity on the hepatic LDL receptor-mediated pathway, PCSK9 has been, however, associated with vascular inflammation in atherogenesis. Indeed, PCSK9 is expressed by various cell types that are involved in atherosclerosis (e.g. endothelial cells, smooth muscle cells and macrophages) and is detected inside human atherosclerotic plaques. We here analyse the biology of PCSK9 and its possible involvement in molecular processes involved in atherosclerosis, beyond the regulation of circulating LDL cholesterol levels.
-
6.
MicroRNA regulation of cholesterol metabolism.
Citrin, KM, Fernández-Hernando, C, Suárez, Y
Annals of the New York Academy of Sciences. 2021;(1):55-77
-
-
Free full text
-
Abstract
MicroRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level. Since many microRNAs have multiple mRNA targets, they are uniquely positioned to regulate the expression of several molecules and pathways simultaneously. For example, the multiple stages of cholesterol metabolism are heavily influenced by microRNA activity. Understanding the scope of microRNAs that control this pathway is highly relevant to diseases of perturbed cholesterol metabolism, most notably cardiovascular disease (CVD). Atherosclerosis is a common cause of CVD that involves inflammation and the accumulation of cholesterol-laden cells in the arterial wall. However, several different cell types participate in atherosclerosis, and perturbations in cholesterol homeostasis may have unique effects on the specialized functions of these various cell types. Therefore, our review discusses the current knowledge of microRNA-mediated control of cholesterol homeostasis, followed by speculation as to how these microRNA-mRNA target interactions might have distinctive effects on different cell types that participate in atherosclerosis.
-
7.
Evaluation of coronary plaques and atherosclerosis using optical coherence tomography.
Shimamura, K, Kubo, T, Akasaka, T
Expert review of cardiovascular therapy. 2021;(5):379-386
Abstract
Introduction: Coronary angiography (CAG) is the standard modality for assessing coronary stenosis; however, it has limitations in assessing coronary plaque morphology. Optical coherence tomography (OCT) is a high-resolution (10-20 μm) light-based intravascular imaging technique that can identify more detailed coronary plaque morphology compared to other intravascular imaging modalities. OCT is remarkable for characterizing fibrous, fibrocalcific, and lipid-rich plaques. The capabilities of OCT are well suited for discriminating three types of unstable plaque morphologies underlying coronary thrombosis, such as plaque rupture, erosion, and calcified nodules. The high resolution of OCT makes it possible to identify important features of vulnerable plaques, such as thin-cap (<65 μm thick) fibroatheroma, macrophages, vasa vasorum, and cholesterol crystals.Areas covered: This review summarizes the clinical impact of OCT and its efficacy in identifying plaque components and morphological features associated with plaque vulnerability.Expertopinion: The unique properties of OCT as a tool for investigating high-risk lesions have greatly contributed to a better understanding of plaque vulnerability. Consequently, OCT has led to significant changes in medical treatment and percutaneous coronary intervention strategies for acute coronary syndrome. Further development and investigation of OCT are necessary to better predict and manage acute coronary events in the future.
-
8.
Dyslipidemia and prevention of atherosclerotic cardiovascular disease in the elderly.
Lucchi, T
Minerva medica. 2021;(6):804-816
Abstract
The atherosclerotic cardiovascular disease (ASCVD) represents the leading cause of death and disability in the elderly. The study of atherosclerosis and the strategies to control ASCVD are evolving. All strategies emphasize the need to lower LDL cholesterol (LDL-C) through an appropriate lifestyle and the use of lipid-lowering drugs, mainly statins. Available evidence coming from clinical trials is useful to inform clinical choices, but the older people are poorly represented in those trials. Thus, evidence supporting the benefit of statin therapy for primary and secondary prevention of fatal and nonfatal ASCVD events in adults aged 75 years and older are limited. The pharmacological therapy of dyslipidemia is recommended by guidelines provided by international expert panels in adults, while in the elderly it is still a matter of debate. Statins are generally well tolerated drugs but their use in the elderly, especially in fragile ones or with multi-pathology that take many other drugs, requires a careful evaluation of the risk-benefit ratio and a shared decision- making process between doctor and patient.
-
9.
High Density Lipoprotein Cholesterol Efflux Capacity and Atherosclerosis in Cardiovascular Disease: Pathophysiological Aspects and Pharmacological Perspectives.
Adorni, MP, Ronda, N, Bernini, F, Zimetti, F
Cells. 2021;(3)
Abstract
Over the years, the relationship between high-density lipoprotein (HDL) and atherosclerosis, initially highlighted by the Framingham study, has been revealed to be extremely complex, due to the multiple HDL functions involved in atheroprotection. Among them, HDL cholesterol efflux capacity (CEC), the ability of HDL to promote cell cholesterol efflux from cells, has emerged as a better predictor of cardiovascular (CV) risk compared to merely plasma HDL-cholesterol (HDL-C) levels. HDL CEC is impaired in many genetic and pathological conditions associated to high CV risk such as dyslipidemia, chronic kidney disease, diabetes, inflammatory and autoimmune diseases, endocrine disorders, etc. The present review describes the current knowledge on HDL CEC modifications in these conditions, focusing on the most recent human studies and on genetic and pathophysiologic aspects. In addition, the most relevant strategies possibly modulating HDL CEC, including lifestyle modifications, as well as nutraceutical and pharmacological interventions, will be discussed. The objective of this review is to help understanding whether, from the current evidence, HDL CEC may be considered as a valid biomarker of CV risk and a potential pharmacological target for novel therapeutic approaches.
-
10.
Mitochondrial Dysfunction in Vascular Wall Cells and Its Role in Atherosclerosis.
Salnikova, D, Orekhova, V, Grechko, A, Starodubova, A, Bezsonov, E, Popkova, T, Orekhov, A
International journal of molecular sciences. 2021;(16)
Abstract
Altered mitochondrial function is currently recognized as an important factor in atherosclerosis initiation and progression. Mitochondrial dysfunction can be caused by mitochondrial DNA (mtDNA) mutations, which can be inherited or spontaneously acquired in various organs and tissues, having more or less profound effects depending on the tissue energy status. Arterial wall cells are among the most vulnerable to mitochondrial dysfunction due to their barrier and metabolic functions. In atherosclerosis, mitochondria cause alteration of cellular metabolism and respiration and are known to produce excessive amounts of reactive oxygen species (ROS) resulting in oxidative stress. These processes are involved in vascular disease and chronic inflammation associated with atherosclerosis. Currently, the list of known mtDNA mutations associated with human pathologies is growing, and many of the identified mtDNA variants are being tested as disease markers. Alleviation of oxidative stress and inflammation appears to be promising for atherosclerosis treatment. In this review, we discuss the role of mitochondrial dysfunction in atherosclerosis development, focusing on the key cell types of the arterial wall involved in the pathological processes. Accumulation of mtDNA mutations in isolated arterial wall cells, such as endothelial cells, may contribute to the development of local inflammatory process that helps explaining the focal distribution of atherosclerotic plaques on the arterial wall surface. We also discuss antioxidant and anti-inflammatory approaches that can potentially reduce the impact of mitochondrial dysfunction.