Abstract
Atherosclerosis (AS) is a chronic inflammatory disease of the arterial intima. As AS represents the most common type of vascular disease, it affects millions of individuals and is a source of high morbidity and mortality rates worldwide. Overwhelming evidence indicates that AS-related inflammation is mediated by proinflammatory cytokines, chemokines, adhesion molecules and inflammatory signaling pathways, with each of these factors being shown to play critical roles during the entire progression of AS. While a number of drugs have been approved for use in the treatment of AS, their benefits are modest, which underscores the urgency for the development of new drug therapies. In part, these deficits in effective drugs can be attributable to the lack of a clear understanding of the molecular mechanisms of AS. In this study, we investigate the capacity for thrombin to trigger inflammation and induce cell proliferation in vascular smooth muscle cells (VSMCs). We then assessed the effects of baicalin and its potential mechanisms on VSMC inflammation as induced by thrombin. Baicalin, which is a natural bioactive compound of S. baicalensis Georgi (SBG), exerted a protective effect against thrombin-induced VSMC inflammation as resulting from the upregulation of PAR-1. This protection as exerted by baicalin appears to reside in its capacity to produce an inhibitory effect on the thrombin-induced activation of the ERK1/2 pathway. These findings suggest that baicalin may be a promising candidate for the treatment of atherosclerosis.
Highlights
Arteriosclerosis (AS), one of the most common types of vascular disease, has become the focus of extensive basic and clinical research due to the serious nature of its effects upon cardiovascular and cerebrovascular diseases [1]
Since thrombin has been identified as a serine protease that activates protease-activated receptors (PARs)-1 to trigger intracellular signaling pathways promoting cell inflammation, we investigated the effect of baicalin on the upregulation of PAR-1 in thrombin-induced vascular smooth muscle cells (VSMCs) inflammation
A possible mechanism for this effect of baicalin may involve an inhibition in the thrombin-induced activation of ERK1/2 signaling in VSMCs, thereby inhibiting VSMC inflammation mediated by thrombin-induced upregulation of PAR-1in AS
Summary
Arteriosclerosis (AS), one of the most common types of vascular disease, has become the focus of extensive basic and clinical research due to the serious nature of its effects upon cardiovascular and cerebrovascular diseases [1]. Overwhelming evidence has accrued indicating that AS is a chronic inflammatory disease, involving different cell types, multiple cytokines and adhesion molecules [2]. Have recently proposed that thrombin, as a component of the coagulation-inflammation axis, is a key factor in regulating the inflammatory processes of AS [4]. Thrombin is a procoagulant and proinflammatory serine protease [5]. It acts as a powerful modulator of many processes involving regulation of permeability, migration and proliferation of VSMCs, induction of multiple proinflammatory markers and recruitment of monocytes into the vascular lesions, all of which are related to the progression of AS [6, 7]. Unlike its activity within the coagulation cascade, its cellular pro-inflammatory and proatherogenic
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