Vascular stiffness in insulin resistance and obesity

Guanghong Jia, Annayya R Aroor, Vincent G DeMarco, Luis A Martinez-Lemus, Gerald A Meininger, James R Sowers, Guanghong Jia, Annayya R Aroor, Vincent G DeMarco, Luis A Martinez-Lemus, Gerald A Meininger, James R Sowers

Abstract

Obesity, insulin resistance, and type 2 diabetes are associated with a substantially increased prevalence of vascular fibrosis and stiffness, with attendant increased risk of cardiovascular and chronic kidney disease. Although the underlying mechanisms and mediators of vascular stiffness are not well understood, accumulating evidence supports the role of metabolic and immune dysregulation related to increased adiposity, activation of the renin angiotensin aldosterone system, reduced bioavailable nitric oxide, increased vascular extracellular matrix (ECM) and ECM remodeling in the pathogenesis of vascular stiffness. This review will give a brief overview of the relationship between obesity, insulin resistance and increased vascular stiffness to provide a contemporary understanding of the proposed underlying mechanisms and potential therapeutic strategies.

Keywords: cardiovascular disease; insulin resistance; obesity; vascular resistance.

Figures

Figure 1
Figure 1
Proposed mechanisms of vascular stiffness in obesity, insulin resistance, and type 2 diabetes. EC, endothelial cell; VSMC, vascular smooth muscle cell; AGE, advanced glycation end products; MMPs, matrix metalloproteinase; TG2, tissue transglutaminase; Ang II, angiotensin II; MR, mineralocorticoid receptor; TxA2, thromboxane A2; ENaC, epithelial Na+ channel; IL, interleukin; TNF, tumor necrosis factor; NO, nitric oxide; MCP-1, monocyte chemotactic protein-1; CRP, C- reactive protein; TGF-β, transforming growth factor- β.

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