Haeme oxygenase signalling pathway: implications for cardiovascular disease

Abstract

Evidence now points to the haeme oxygenase (HO) pathway as a possible actor in modulating risk for cardiovascular disease (CVD). In particular, the HO pathway may represent a key endogenous modulator of oxidative, inflammatory, and cytotoxic stress while also exhibiting vasoregulatory properties. In this review, we summarize the accumulating experimental and emerging clinical data indicating how activity of the HO pathway and its products may play a role in mechanisms underlying the development of CVD. We also identify gaps in the literature to date and suggest future directions for investigation. Because HO pathway activity can be influenced not only by genetic traits and environmental stimuli but also by a variety of existing pharmacologic interventions, the pathway could serve as a prime target for reducing the overall burden of CVD. Further work is needed to determine the role of HO pathway products as possible prognostic markers of risk for clinical CVD events and the extent to which therapeutic augmentation or inhibition of HO pathway activity could serve to modify CVD risk.

Association of Exhaled Carbon Monoxide With Stroke Incidence and Subclinical Vascular Brain Injury

“…8 Heme oxygenase-1 (HO-1) is an increasingly recognized modulator of cardiovascular risk and its expression is inducible by physiologic stressors such as circulating phospholipids, vascular injury, hypertension, hyperglycemia, smoking, and laminar shear stress. 8, 33-36 In autopsy samples of human coronary arteries, HO-1 activity was shown to be overexpressed in atherosclerotic plaques and to correlate with the degree of stenosis. 37 HO-1 has also been demonstrated to be an essential driver of insulin resistance.…”

“…8 In animal models, physiologic concentrations of CO in vivo promote vascular and endothelial integrity, 9, 10 prevent hypoxia-induced apoptosis, 11 and attenuate the development of obesity. 12 By contrast, elevated endogenous CO concentrations have been found to antagonize NO-mediated vasodilation, 13 promote hyperglycemia, 14 foster oxidative stress, 15 and mediate the hypertensive response to physiologic stress in several disease models.…”

Oxidative stress and antioxidant treatment in patients with peripheral artery disease

“…; Durante ; Fredenburgh et al. ). HO‐1 has also been shown to be significantly reduced in PAD patients, and has been implicated as an independent predictor of PAD (Signorelli et al.…”

“…Bilirubin can protect against oxidation of lipids, and its antioxidant effect exceeds that of vitamin E toward lipid peroxidation (Stocker et al 1987;Sedlak and Snyder 2004). In addition to its protective role against oxidative stress, HO-1 also contributes to angiogenesis, and the HO-1 signaling pathway has been implicated in modulating the risk for cardiovascular diseases (Idriss et al 2008;Durante 2010;Fredenburgh et al 2015). HO-1 has also been shown to be significantly reduced in PAD patients, and has been implicated as an independent predictor of PAD (Signorelli et al 2016).…”

Regarding sex differences in cardiovascular ageing: let us not forget iron

“…We also find intriguing the possibility that iron depletion in menstruating women may be cardioprotective. We had previously been aware of the potential role of iron as a by-product of haeme oxygenase activity in mediating cardiometabolic risk,2 with a number of community studies having reported equivocal findings when examining the relation between either iron or ferritin with respect to outcomes 3–6. It is our impression that heterogeneity in prior study results may be related to differences in participant sampling methods, the iron measures used (ferritin, total iron-binding capacity, transferrin saturation, serum iron and dietary iron intake) and presence of potential confounding variables that could influence both iron levels and a given outcome of interest (eg, inflammation and genetic variants).…”