Heme Oxygenases in Cardiovascular Health and Disease

Abstract

Heme oxygenases are composed of two isozymes, Hmox1 and Hmox2, that catalyze the degradation of heme to carbon monoxide (CO), ferrous iron, and biliverdin, the latter of which is subsequently converted to bilirubin. While initially considered to be waste products, CO and biliverdin/bilirubin have been shown over the last 20 years to modulate key cellular processes, such as inflammation, cell proliferation, and apoptosis, as well as antioxidant defense. This shift in paradigm has led to the importance of heme oxygenases and their products in cell physiology now being well accepted. The identification of the two human cases thus far of heme oxygenase deficiency and the generation of mice deficient in Hmox1 or Hmox2 have reiterated a role for these enzymes in both normal cell function and disease pathogenesis, especially in the context of cardiovascular disease. This review covers the current knowledge on the function of both Hmox1 and Hmox2 at both a cellular and tissue level in the cardiovascular system. Initially, the roles of heme oxygenases in vascular health and the regulation of processes central to vascular diseases are outlined, followed by an evaluation of the role(s) of Hmox1 and Hmox2 in various diseases such as atherosclerosis, intimal hyperplasia, myocardial infarction, and angiogenesis. Finally, the therapeutic potential of heme oxygenases and their products are examined in a cardiovascular disease context, with a focus on how the knowledge we have gained on these enzymes may be capitalized in future clinical studies.

Ablation of adipose-HO-1 expression increases white fat over beige fat through inhibition of mitochondrial fusion and of PGC1α in female mice

“…Essentially balanced mitochondrial dynamics is important for the maintenance of mitochondrial health, function and energy generation [39], [53]. Concomitantly inhibition of HO activity reduces mitochondrial quality control by inhibition of mitochondrial fusion mediator Mfn1, Mfn2 and Opa1 but activation of mitochondrial fission mediator Fis1 [42], [43].…”

“…While mitochondrial fission is orchestrated by the dynamin-related protein 1 (DRP1) and the mitochondrial fission 1 (Fis1) protein [34], [35], the fusion process is controlled by the autosomal dominant optic atrophy 1 (OPA1) protein, together with the mitochondrial fusion proteins mitofusion 1 and 2 (Mfn 1 and 2), located on the mitochondrial outer membrane, [36], [37]. As HO-1/HO-2 are known regulators of mitochondrial integrity and function [38], [39], [40], [41], we hypothesized that adipose HO-1 gene is essential for increased mitochondrial fusion that may result in an increase in the beige cell population within adipose tissue or conversion of white adipose function populations and white adipose function that include expression of PGC1α levels and thermogenic genes.…”

Preeclampsia: novel insights from global RNA profiling of trophoblast subpopulations

“…HMOX1 up-regulation was consistent with its role in the vasculature and induction by hypoxia. 61 Deletion of a single copy of this gene in mice produces a preeclampsia-like syndrome.…”

Vanillic acid alleviates palmitic acid‐induced oxidative stress in human umbilical vein endothelial cells via Adenosine Monophosphate‐Activated Protein Kinase signaling pathway

“…AMP‐activated protein kinase (AMPK) is a crucial kinase for inhibiting oxidative stress and regulating mitochondrial function. Activation of AMPK upregulates p‐Nrf2 and HO‐1 expression, which achieves vascular protection (Ayer, Zarjou, Agarwal, & Stocker, ).…”