Vascular and Macrophage Heme Oxygenase-1 in Hypertension: A Mini-Review

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.

Impact of Helicobacter pylori-Related Metabolic Syndrome Parameters on Arterial Hypertension

“…Focusing on H. pylori-related inflammatory processes, chronic inflammation due to H. pylori infection [46] activates a variety of mediators (Table 2) that have been linked to MetS-related endothelial cell dysfunction [19,92]. Indeed, H. pylori increases the levels of inflammatory mediators, such as MetS-related tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, IL-8, interferon (IFN)-γ, fibrinogen, thrombin, intercellular adhesion molecule, and vascular cell adhesion molecule; these MetS-related inflammatory mediators directly or indirectly damage the vascular walls, thereby triggering atherosclerosis [39,[93][94][95][96]; H. pylori-mediated inflammation has been linked to atherosclerosis [97]; and the aforementioned inflammatory mediators have been involved in the pathophysiology of MetS-related arterial hypertension [98,99].…”

Heme Oxygenase 1 in Vertebrates: Friend and Foe

“…Heme oxygenase-1 (HO-1) is the inducible form of the enzyme and differs from HO-2 that is constitutively expressed (highest expression in brain and testes) [3]. HO-1 is induced by different stresses/transcription factors and its byproducts possess anti-inflammatory, anti-apoptotic, and antioxidant properties [4]. Furthermore, a truncated form of HO-1 with low enzymatic activity, located in the nucleus, seems to regulate redox-related genes, including Nrf2, the major transcriptional activator of HO-1, suggesting a positive feedback loop [5][6][7].…”

Mechanisms underlying acupuncture therapy in chronic kidney disease: A narrative overview of preclinical studies and clinical trials

“…Renal hypertension induced by ischemic nephropathy is affected by oxidative stress mechanisms involving molecules such as NOS and heme oxygenase (HO-1/2) ( 114 – 116 ). In one study, EA was shown to prevent the reduction of endothelial NOS and nitric NOS levels associated with hypertension ( 53 ).…”