[Coronary microcirculation. Pathophysiology, clinical relevance, and importance for regenerative therapy after...

The coronary microcirculation does not only control perfusion of the myocardium, but also plays an important role for the manifestation of ischemic heart disease throughout all stages of the disease. Risk factors for coronary artery disease are associated with a reduced endothelium-dependent blood flow regulation, which not only may aggravate myocardial ischemia but also determines blood flow-induced shear stress exposed to the vascular wall, modulating the vascular milieu (e. g., by controlling nitric oxide bioactivity) and thereby altering progression of atherosclerosis in conductance vessels. Furthermore, generally impaired microvascular function is predictive of cardiovascular events, e. g., after percutaneous coronary interventions or after an acute myocardial infarction. In the latter case, thrombotic embolism from ruptured plaques in the conductance vessels as well as inflammation and reperfusion injury are the essential components of the microvascular disorder. Interestingly, therapeutic strategies which improve microvascular dysfunction, such as statins in stable coronary artery disease or glycoprotein IIb/IIIa inhibitors during acute myocardial infarction, are associated with an improved long-term prognosis. These facts give promise for new therapeutic principles: experimental data demonstrate, that the therapeutic application of stem or progenitor cells after an acute myocardial infarction induces growth of new microvessels (neovascularization) and thereby improves microvascular perfusion, which may favorably alter infarct expansion and remodeling. First clinical data, demonstrating indeed an improved coronary blood flow regulation after progenitor cell therapy in patients with ischemic heart disease, have to be established by further clinical trials.