Local proliferation dominates lesional macrophage accumulation in atherosclerosis

During the inflammatory response that drives atherogenesis, macrophages accumulate progressively in the expanding arterial wall(1,2). The observation that circulating monocytes give rise to lesional macrophages(3–9) has reinforced the concept that monocyte infiltration dictates macrophage build-up. Recent work indicates, however, that macrophages do not depend on monocytes in some inflammatory contexts(10). We therefore revisited the mechanism of macrophage accumulation in atherosclerosis. We show that murine atherosclerotic lesions experience a surprisingly rapid, 4-week, cell turnover. Replenishment of macrophages in these experimental atheromata depends predominantly on local macrophage proliferation rather than monocyte influx. The microenvironment orchestrates macrophage proliferation via the involvement of scavenger receptor (SR)-A. Our study reveals macrophage proliferation as a key event in atherosclerosis and identifies macrophage self-renewal as a therapeutic target for cardiovascular disease

Proteomics of acute coronary syndromes.

Acute coronary syndromes (ACS), such as unstable angina, acute myocardial infarction, and sudden cardiac death, are commonly associated with the presence of vulnerable plaques in coronary arteries. Rupture or erosion of vulnerable plaques results in the formation of luminal thrombi due to the physical contact between platelets and thrombogenic elements within the atherosclerotic lesions. Considering the socioeconomic burden of ACS, it is imperative that the scientific community achieves a clear understanding of the multifaceted pathophysiology of vulnerable atheroma to identify accurate prognostic biomarkers and therapeutic targets. The analytical power of modern proteomic technologies could facilitate our understanding of vulnerable plaques and lead to the discovery of novel therapeutic targets and diagnostic biomarkers

The extracellular matrix can regulate vascular cell migration, proliferation, and survival: relationships to vascular disease

The extra cellular matrix (ECM) of the normal artery wall is a collection of fibrous proteins and associated glycoproteins embedded in a hydrated ground substance of glycosaminoglycans and proteoglycans. These distinct molecules are organized into a highly ordered network that are closely associated with the vascular cells that produce them. In addition to providing the architectural framework for the artery wall that imparts mechanical support and viscoelasticity, the ECM can regulate the behaviour of vascular cells, including their ability to migrate, proliferate and survive injury. The composition of the ECM is different within intimal lesions of atherosclerosis, which are composed of monocytes and lymphocytes from the circulation and smooth muscle cells (SMC) that migrate from the media to the intima (Ross 1993, 1999), and these differences may contribute to the altered phenotype of vascular cells within lesions. This review will briefly outline the ECM changes observed in atherosclerosis and restenosis and the potential relationship of these changes to altered vascular cell functions