Pathogenic involvement of the microvasculature in cardiovascular disease

Microvascular abnormalities are associated with the common types of cardiov ascular disease. In some they are consequences of the disease, but in a num ber of them, including hypertension, they appear to be involved in pathogen esis and thus are potential targets for therapeutic intervention. Arteriolo sclerosis and microvascular rarefaction occur in systemic hypertension. Alt hough the former is reversible with treatment, recovery from the latter may be age-dependent. Angiogenesis inadequately compensates for myocardial hyp ertrophy due to pressure overload, and the loss of coronary reserve eventua lly leads to focal ischaemic necrosis and heart failure. Angiogenic therapy has the potential to prevent myocyte loss in this situation. In contrast, ischaemia and reperfusion in the myocardium are accompanied by partial or c omplete loss of microvascular competence which compromises post-ischaemic r ecovery. This microvascular stunning appears to be caused by oxygen radical -induced endothelin release and leukocyte activation. In atherosclerosis a microvascular plexus develops within the lesions, and the microcirculation downstream shows impaired post-ischaemic hyperaemia and endothelium-depende nt vasodilatation. The latter dysfunctions are reversed when the hyperlipid aemia is controlled and are thus consequences of atherosclerosis. Thus, the common types of cardiovascular disease are associated with distinct forms of microvascular pathology and new therapies will therefore need to be corr espondingly diverse.