Innate and Adaptive Inflammation as a Therapeutic Target in Vascular Disease

Abstract

Atherosclerosis, the main pathophysiological condition leading to cardiovascular disease (CVD), is now considered to be a chronic inflammatory condition. Statins are the most widely used and promising agents in treating CVD and are renowned for their pleiotropic lipid-lowering independent effects. Statins exert their anti-inflammatory effects on the vascular wall through a variety of molecular pathways of the innate and adaptive immune systems, their impact on the circulating levels of pro-inflammatory cytokines, and their effect on adhesion molecules. By inhibiting the mevalonate pathway and isoprenoid formation, statins account for the increase of nitric oxide bioavailability and the improvement of vascular and myocardial redox state by multiple different mechanisms (directly or indirectly through low-density lipoprotein [LDL] lowering). A large number of randomized control trials have shown that statins help in the primary and secondary prevention of cardiovascular events, not only via their lipid-lowering effect, but also due to their anti-inflammatory potential as well. In this paper, we examine the molecular pathways in which statins are implicated and exert their anti-inflammatory effects, and we focus specifically on their impact on innate and adaptive immunity systems. Finally, we review the most important clinical data for the role of statins in primary and secondary prevention of cardiovascular events.

PTPRO Promotes Oxidized Low-Density Lipoprotein Induced Oxidative Stress and Cell Apoptosis through Toll-Like Receptor 4/Nuclear Factor κB Pathway

“…AS commonly initiates within the arterial wall primarily as a result of the destruction occurring in endogenously structures, which can be attributed to several matters, such as hypertension, smoking, oxidized low-density lipoprotein (ox-LDL) and so forth [3-5]. Ox-LDL, as the most important factor contributing to the development of AS, can activate both the innate and adaptive immune responses with the differentiation from monocytes to macrophages and the unregulated phagocytic activity of macrophages [6-8], subsequently induce the accumulation of lipid and the formation of foam cells, which is the hallmark event of AS [9, 10]. …”

Role of angiotensin II in experimental Venezuelan equine encephalitis in rats

“…The main vascular features of the inflammatory response are vasodilation, increased vascular permeability, endothelial expression of adhesion molecules, and chemokine production [38]. Accordingly, an increased number of dilated capillaries and increased expression of ICAM-1 Fig.…”

Stabilization of high-risk plaques

“…It has been reported that statins promote the differentiation of Tregs (212), and restrain the differentiation of Th 17 (213). Kruppel-like factor 2 (KLF2), which regulates the expression of molecules essential for naive T cell recirculation and the maintenance of T cell quiescence, plays a key role in this mechanism (214).…”