Chronic obstructive pulmonary disease and atherosclerosis: common mechanisms and novel therapeutics

Figures

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  Figure 1. Flow-mediated vasoconstrictive and vasodilatory mechanisms Luminal shear stress promotes Ang II-mediated vasoconstriction through the binding and activation of the Ang II–AT1 G-protein coupled receptor complex, inhibiting the sarcomere phosphatase brake of MLCP and enhancing MLCK activity, promoting smooth muscle-dependent vasoconstriction. Shear stress may also induce vasodilation through EC-mediated NO production and release, driving the activity of guanylyl cyclase within the VSMCs and thus endothelial-dependent vasodilation occurring.

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  Figure 2. The role of CS and COPD in atherogenesis Exposure to CS promotes pulmonary inflammation and COPD pathogenesis due to over-exuberant ROS and immune cell recruitment into the lungs. These harmful inflammatory mediators and ROS can then spill into the blood leading to a systemic inflammatory response driving various extrapulmonary pathologies including atherosclerosis, MI as well as altering the metabolic activity of the liver, driving inflammation and the oxidation of low-density lipoprotein (LDL).

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  Figure 3. Atherogenesis, plaque rupture and thrombosis Enhanced shear stress, turbid blood flow, BP and inflammation mediate the formation of an atherosclerotic lesion. This then promotes the recruitment of immune cells, proliferation and accumulation of VSMCs and the oxidative modification of LDL to form harmful foam cells, a key component of the necrotic core of the lesion. Upon plaque rupture, a blood clot is formed, and thrombus formation occurs, making these patients highly susceptible to a further cardiovascular event.