Thrombosis formation on atherosclerotic lesions and plaque rupture

Abstract

Atherosclerosis is a silent chronic vascular pathology that is the cause of the majority of cardiovascular ischaemic events. The evolution of vascular disease involves a combination of endothelial dysfunction, extensive lipid deposition in the intima, exacerbated innate and adaptive immune responses, proliferation of vascular smooth muscle cells and remodelling of the extracellular matrix, resulting in the formation of an atherosclerotic plaque. High-risk plaques have a large acellular lipid-rich necrotic core with an overlying thin fibrous cap infiltrated by inflammatory cells and diffuse calcification. The formation of new fragile and leaky vessels that invade the expanding intima contributes to enlarge the necrotic core increasing the vulnerability of the plaque. In addition, biomechanical, haemodynamic and physical factors contribute to plaque destabilization. Upon erosion or rupture, these high-risk lipid-rich vulnerable plaques expose vascular structures or necrotic core components to the circulation, which causes the activation of tissue factor and the subsequent formation of a fibrin monolayer (coagulation cascade) and, concomitantly, the recruitment of circulating platelets and inflammatory cells. The interaction between exposed atherosclerotic plaque components, platelet receptors and coagulation factors eventually leads to platelet activation, aggregation and the subsequent formation of a superimposed thrombus (i.e. atherothrombosis) which may compromise the arterial lumen leading to the presentation of acute ischaemic syndromes. In this review, we will describe the progression of the atherosclerotic lesion along with the main morphological characteristics that predispose to plaque rupture, and discuss the multifaceted mechanisms that drive platelet activation and subsequent thrombus formation. Finally, we will consider the current scientific challenges and future research directions.

High Levels of (Un)Switched Memory B Cells Are Associated With Better Outcome in Patients With Advanced Atherosclerotic Disease

“…Its main underlying pathology, atherosclerosis, is an inflammatory lipid disorder and the major cause of acute cardiovascular syndromes 2, 3, 4. Many inflammatory cell types, including monocytes, macrophages, mast cells, neutrophils, and T and B cells, have been implicated in the initiation, progression, and destabilization of atherosclerosis 5.…”

ApoA1 and ApoA1-specific self-antibodies in cardiovascular disease

“…Plaque rupture leads to thrombus formation followed by late atherosclerotic complications such as acute coronary syndrome (ACS), acute myocardial infarction (MI), stroke, and thromboembolism. 4 Inflammation has a crucial role on all stages of atherogenesis starting from the transendothelial trafficking of leukocytes in initial steps of atherosclerosis until the plaque rupture. Inflammatory responses regulate overproduction and activity of MMPs involved in pathological arterial wall remodeling and fibrous cup thickening.…”

CD98 Regulates Vascular Smooth Muscle Cell Proliferation in Atherosclerosis

“…Male mice of each genotype, [8][9][10] weeks old, were put on HFD for 16 weeks to allow the establishment of VSMC-rich atherosclerotic plaque.…”

“…Advanced atherosclerotic plaques are characterized by the presence of fibrous cap, composed of VSMC and collagen, especially collagen type VIII 3 , that surrounds and stabilizes the center core of the plaque, reducing the risk of plaque rupture and its consequences 1,4,7 . On the other hand, VSMC apoptosis leads to drastic vessel remodeling, with increased inflammation and coagulation, and thinning of the fibrous cap, making the plaque more prone to rupture 8,9 .…”