Inflammation at the Molecular Interface of Atherogenesis

Abstract

Despite the multifactorial nature of atherosclerosis, substantial evidence has established inflammation as an often surreptitious, yet critical and unifying driving force which promotes disease progression. To this end, research has defined molecular networks initiated by cytokines, growth factors and other proinflammatory molecules which promote hallmarks of atherosclerosis such as endothelial dysfunction, macrophage infiltration, LDL oxidation, cell proliferation and thrombosis. Although commonly associated with risk factors such as dyslipidemia, diabetes and hypertension, the global etiology of atherosclerosis may be alternatively attributed to underlying anthropological pressures. The agricultural, industrial and technological revolutions produced alterations in dietary, social and economic factors which have collectively exaggerated the exposure of the human genome to environmental stimuli. Furthermore, advances in sanitation, nutrition, and medicine have increased the lifespan of humans, effectively prolonging blood vessel exposure to these factors. As a result, the vasculature has become conditioned to respond to injury with what is arguably an overzealous immunological response; thus setting the stage for the prevalence of cardiovascular disease, including atherosclerotic plaque development in Western populations. Evidence suggests that each of these alterations can be linked to specific mediators in the inflammatory process. Integration of these factors with an inflammationbased hypothesis of atherosclerosis has yet to be extrapolated to observations in the realms of basic and clinical sciences and is the focus of this review. (Am J Pathol

Association of Interleukin-6 With the Progression of Carotid Atherosclerosis

“…IL-6 not only stimulates the secretion of acute phase proteins such as hs-CRP 29 but also promotes a variety of atherosclerotic mechanisms such as endothelial dysfunction, recruitment and activation of other inflammatory cells, and oxidation of lipoproteins. 1,3,30 Therefore, the circulating IL-6 level could be more closely associated with the progression of atherosclerosis than the level of downstream factors such as hs-CRP.…”

Advanced Glycation End Products: A Molecular Target for Vascular Complications in Diabetes

“…There is a growing body of evidence, ranging from in vitro experiments to pathologic analysis and epidemiologic studies suggesting that atherosclerosis is intrinsically an inflammatory disease (31,32). Activation of the AGE-RAGE axis results in generation of intracellular oxidative stress generation and subsequent activation of NF-κB in vascular wall cells, which could promote a variety of atherosclerosis/inflammation-related gene expression, thereby contributing to the development and progression of CVD in diabetes (2,(23)(24)(25)(26)(27).…”

Combination of amlodipine and atorvastatin synergistically reduces leukocyte recruitment to mechanically injured mouse femoral artery

“…[1][2][3] Co-treatment with the HMG-CoA reductase inhibitors (statins) and calcium channel blockers (CCBs) significantly contributed to the reduction of cardiovascular events. [4][5][6][7][8][9] The AngloScandinavian Cardiac Outcomes Trial-Lipid Lowering Arm recently documented a striking efficacy of adding atorvastatin to hypertensive patients without obvious dyslipidemia.…”