- Prof. Giovanni Cimmino
- Department of Translational Medical Sciences, Division of Cardiology, University of Campania “Luigi Vanvitelli”, Naples, Italy.
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Special Issue Introduction
In the last two decades, our understanding of the molecular mechanisms involved in the formation, progression and complication of atherosclerosis has significantly advanced. The key role of inflammation and immunity in this phenomenon has now been largely accepted and documented. Accumulating evidence highlights the activation of different inflammatory pathways and the involvement of different immune cells, such as monocytes and T-lymphocytes, in the pathophysiology of atherosclerosis, particularly in contributing to plaque complications, such as rupture or ulceration/erosion. Once complicated, intralesional prothrombotic material, such as tissue factor, is exposed to the flowing blood, thus activating coagulation cascade and platelet aggregation, ultimately leading to acute thrombus formation within the coronary vessel. This represents the key event underlying the clinical manifestations of acute coronary syndromes (ACS). Vulnerable plaques contain more inflammatory and immune cells than stable plaques; these cells often infiltrate the atherosclerotic lesion adjacent to the site of fibrous cap rupture and around the lipid core, as well as in the adventitia around areas of neovascularization, suggesting a causative role in plaque complication. A highly dynamic and coordinated immune response occurs in atherosclerosis as well as in ischemic cardiac tissue, which is dependent not only on macrophages but also on leukocytes, both resident and newly recruited from the blood flow. Once activated within the atherosclerotic lesion, macrophages become a source of inflammatory mediators that amplify the inflammatory cycle by recruiting more macrophages as well as B and T-lymphocytes. Although numerically T-cells represent a minority of the leukocytes present in plaques, several reports support their decisive regulatory role within atherosclerotic lesion. Specifically, as master cells of the adaptive immune response, they act like the director of an orchestra, instructing the more abundant monocytic effectors. On the other hand, recruitment of T-cells perpetuates the inflammatory process via release of other cytokines, thus amplifying local inflammation. Recent studies indicate T-cells also contribute to vascular thrombosis via expression of functional tissue factor. Intraplaque antigens and local cytokines microenvironment will define the immune-inflammatory response and cells phenotype, thus determining the switch of an atherosclerotic plaque from stable to vulnerable lesion. Combination of all these factors, such as local and systemic mediators, degrees of inflammation, types of cell infiltration, rheological characteristics of blood flow at the site of plaque rupture and thrombogenic substrates within the atherosclerotic lesion will define the severity of clinical picture.
KeywordsAtherosclerosis, coagulation, immunity, inflammation, thrombosis
Submission Deadline15 Jun 2021