Cardiovascular Diseases (CVD), are the leading cause of human mortality worldwide and the focus of
the intensive investigation is to characterize their pathogenesis. This review examines contribution to CVD of
heme oxygenases (HOs), heat shock protein enzymes, comprising 3 isoforms: HO-1 (inducible), HO-2 (constitutively
expressed) and HO-3 (function presently undefined), which constitute a primary endogenous countermeasure
to oxidative tissue damage. Their role as CVD countermeasures is considered in the context of atherosclerosis,
consequences of which are the leading cause of CVD deaths and from which 5 major syndromes may develop,
namely: coronary artery disease and stroke, peripheral artery disease, kidney disease, cardiopulmonary disease
and cerebrovascular disease. Over 75% of CVD deaths result from Coronary artery disease and stroke, with
the severity of these conditions correlating with a systemic increase of the endogenous antioxidant bilirubin,
produced by HO degradation of heme. Peripheral artery disease, (PAD) resulting from constricted arteries of the
extremities is a painful and disabling condition, the severity of which correlates with elevated serum HO. Whether
this represents an adaptive response or the enzyme is a contributor to PAD, remains to be determined. CVD
symptoms, particularly hypertension, damage the vasculature and filtering structures of the kidneys and may be
ameliorated by HO inducers. Interestingly, constitutive renal expression of HO-2 indicates that the enzyme is
vital for healthy kidney function. Right ventricular hypertrophy and increased vascular resistance in blood vessels
of the lungs exhibit mutually reinforcing positive feedback to result in cardiopulmonary heart disease, with morbidity
and mortality resulting from associated inflammation and may be decreased with HO-1 inducers. Cerebrovascular
disease, a major CVD complication affecting brain vasculature, with resulting susceptibility to stroke,
maybe potently ameliorated by HO-1 inducers.
Conclusion:
Each of the six major categories of CVD exhibit features of pathogenesis that hold potential as future
therapeutic targets, for modulated heme oxygenase activity.