Abstract
Hypertension is one predictive factor for stroke and heart ischemic disease. Nowadays, it is considered an inflammatory disease with elevated cytokine levels, oxidative stress, and infiltration of immune cells in several organs including heart, kidney, and vessels, which contribute to the hypertension-associated cardiovascular damage. Macrophages, the most abundant immune cells in tissues, have a high degree of plasticity that is manifested by polarization in different phenotypes, with the most well-known being M1 (proinflammatory) and M2 (anti-inflammatory). In hypertension, M1 phenotype predominates, producing inflammatory cytokines and oxidative stress, and mediating many mechanisms involved in the pathogenesis of this disease. The increase in the renin–angiotensin system and sympathetic activity contributes to the macrophage mobilization and to its polarization to the pro-inflammatory phenotype. Heme oxygenase-1 (HO-1), a phase II detoxification enzyme responsible for heme catabolism, is induced by oxidative stress, among others. HO-1 has been shown to protect against oxidative and inflammatory insults in hypertension, reducing end organ damage and blood pressure, not only by its expression at the vascular level, but also by shifting macrophages toward the anti-inflammatory phenotype. The regulatory role of heme availability for the synthesis of enzymes involved in hypertension development, such as cyclooxygenase or nitric oxide synthase, seems to be responsible for many of the beneficial HO-1 effects; additionally, the antioxidant, anti-inflammatory, antiapoptotic, and antiproliferative effects of the end products of its reaction, carbon monoxide, biliverdin/bilirubin, and Fe2+, would also contribute. In this review, we analyze the role of HO-1 in hypertensive pathology, focusing on its expression in macrophages.
Highlights
Hypertension is an important risk factor that significantly contributes to worldwide cardiovascular morbidity and mortality
carbon monoxide (CO) downregulates proinflammatory cytokine production, including tumor necrosis factor-α (TNF-α), IL-1β, and macrophage inflammatory protein-1β (MIP-1β); simultaneously, CO increases IL-10 expression, leading to anti-inflammatory tissue protection, which is dependent on the modulation of mitogen-activated protein kinase (MAPK) activities (Otterbein et al, 2000)
Oxidative stress and inflammation highly contribute to hypertensive alterations, and macrophage polarization to inflammatory phenotype plays a key role in those processes
Summary
Hypertension is an important risk factor that significantly contributes to worldwide cardiovascular morbidity and mortality. A relationship between inflammation and hypertension-associated damage has been reported Both the adaptive immunity (Xiao and Harrison, 2020) and cells from the innate immune system, such as macrophages, have been described to be involved in hypertension. Increased macrophage infiltration has been observed in different hypertension models (Norlander et al, 2018; Caillon et al, 2019) and a causal role of monocytes and macrophages in the hypertension development and the associated vascular alterations has been described (De Ciuceis et al, 2005). ROS are mainly produced in the mitochondria and by NADPH oxidase, and by uncoupled NO synthase and xanthine oxidase These sources are activated in endothelial, vascular smooth muscle (VSMC), neuronal, and renal tubular cells (Xiao and Harrison, 2020). This review will describe the role of HO-1 and its enzymatic products in hypertension, focusing on its expression in macrophages
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