Abstract
Background. The NF-E2–related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway has an emerging role in atherosclerosis. Activated by oxidative stress, it is deemed to exert athero-protective effects. We aimed at evaluating the relationships between plasma HO-1, clinical/molecular profiles and coronary disease patterns in patients with chronic coronary syndromes (CCS). Methods. HO-1 was measured in 526 patients (60 ± 9 years, 318 males) with CCS. Coronary computed tomography angiography (CTA) and stress imaging were used to assess the disease phenotype (coronary atherosclerosis and myocardial ischemia) in a subgroup of 347 patients. Results. In the overall population, HO-1 median value (25–75 percentile) was 5.195 (1.75–8.25) ng/mL. Patients with higher HO-1 were more frequently male, had a higher BMI and lower LVEF%, but otherwise similar risk factors than the other patients. Their bio-humoral profile was characterized by higher markers of endothelial/myocardial dysfunction, but lower levels of cholesterol lipoproteins. Coronary artery disease was characterized by more diffuse atherosclerosis, with mainly non-obstructive and calcified plaques, and a higher prevalence of functional ischemia. Conclusion: In patients with CCS, higher plasma HO-1 levels are associated with lower cholesterol and a more diffuse but mainly non-obstructive coronary atherosclerosis, confirming a potential role for the Nrf2/HO-1 pathway as a protective feedback.
Highlights
Cardiovascular disease (CVD) accounts for the largest proportion of deaths in Western Countries [1]
It has been very recently reported that activation of the nuclear erythroid factor 2–related factor 2 (Nrf2)/HO-1 pathway in a hepatic cell line by phytochemical dietary supplementation decreased the expression of two genes involved in cholesterol metabolism, 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR), that catalyzes the rate-limiting step in the biosynthesis of cholesterol and is the target of the statin family of drugs, and PCSK9, that can bind to the LDL-C receptor (LDLR), causing LDL-C to be degraded rather than recycled, with the effect of slowing cholesterol removal [21]
HO-1 levels and a bio-humoral and imaging coronary phenotype mainly characterized by reduced cholesterol and a more diffuse coronary atherosclerosis, but with mainly nonobstructive and calcified plaques
Summary
Cardiovascular disease (CVD) accounts for the largest proportion of deaths in Western Countries [1]. Atherosclerosis, the main underlying pathological basis for CVD, is a chronic disease with complex pathogenesis [2], with endothelial dysfunction, inflammation, lipid deposition, and oxidative stress involved in the initiation and progression of atherosclerosis [3,4,5]. Antioxidant defenses reported to be associated with atherosclerosis include the activation of nuclear erythroid factor 2–related factor 2 (Nrf2)/Heme. HO-1 has a pivotal role in the antioxidant mechanism within the cell, promoting the degradation of the prooxidant heme to carbon monoxide, biliverdin, and ferrous ion [7,8]. HO-1 is involved in protective mechanisms in several pathological conditions, including endothelial dysfunction, inflammation, atherosclerosis, and myocardial ischemia/reperfusion injury [9,10,11,12,13]
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