Microvesicles in Atherosclerosis and Angiogenesis: From Bench to Bedside and Reverse

Abstract

Atherosclerosis (AT) is a progressive chronic disease involving lipid accumulation, fibrosis, and inflammation in medium and large-sized arteries, and it is the main cause of cardiovascular disease (CVD). AT is caused by dyslipidemia and mediated by both innate and adaptive immune responses. Despite lipid-lowering drugs have shown to decrease the risk of cardiovascular events (CVEs), there is a significant burden of AT-related morbidity and mortality. Identification of subjects at increased risk for CVE as well as discovery of novel therapeutic targets for improved treatment strategies are still unmet clinical needs in CVD. Microvesicles (MVs), small extracellular plasma membrane particles shed by activated and apoptotic cells have been widely linked to the development of CVD. MVs from vascular and resident cells by facilitating exchange of biological information between neighboring cells serve as cellular effectors in the bloodstream and play a key role in all stages of disease progression. This article reviews the current knowledge on the role of MVs in AT and CVD. Attention is focused on novel aspects of MV-mediated regulatory mechanisms from endothelial dysfunction, vascular wall inflammation, oxidative stress, and apoptosis to coagulation and thrombosis in the progression and development of atherothrombosis. MV contribution to vascular remodeling is also discussed, with a particular emphasis on the effect of MVs on the crosstalk between endothelial cells and smooth muscle cells, and their role regulating the active process of AT-driven angiogenesis and neovascularization. This review also highlights the latest findings and main challenges on the potential prognostic, diagnostic, and therapeutic value of cell-derived MVs in CVD. In summary, MVs have emerged as new regulators of biological functions in atherothrombosis and might be instrumental in cardiovascular precision medicine; however, significant efforts are still needed to translate into clinics the latest findings on MV regulation and function.

Head-to-Head Comparison of the Incremental Predictive Value of The Three Established Risk Markers, Hs-troponin I, C-Reactive Protein, and NT-proBNP, in Coronary Artery Disease

“…Here, we suggest NT-proBNP as a candidate biomarker for risk prediction in patients with CAD, as part of a risk prediction panel including additional biomarkers. Microvesicles, which are small extracellular membrane particles shed by activated and apoptotic cells, have emerged as promising biomarkers for risk prediction not only in many inflammation-associated disorders in general but especially in cardiovascular diseases [24,25]. Although specific roles of each phenotype still remain to be further evaluated, a multipanel approach including NT-proBNP might facilitate risk prediction in CAD patients [26].…”

Electronic cigarettes increase endothelial progenitor cells in the blood of healthy volunteers

“…Indeed, patients with stable carotid plaques, manifest ischemic stroke and myocardial infarction, all exhibit elevated levels of PMVs [132][133][134]. This indicates that endothelial damage is a key cause for PMV mobilization and it has been suggested that activated PMVs seem to play an important role in thrombus formation and in the pathogenesis of atherosclerosis [135].…”

Potential Beneficial Effects of Vitamin D in Coronary Artery Disease

“…More recent investigations have suggested an additional excessive inflammatory response in the subintimal arterial space followed by thrombus formation [2,3]. Furthermore, several studies have found that blood microparticle levels are elevated in individuals with CAD [4,5]. Different molecules on the surface of the microparticles mediate procoagulant properties that may lead to an acute coronary event [6].…”