Tobacco smoking induces cardiovascular mitochondrial oxidative stress, promotes endothelial dysfunction, and enhances hypertension

Abstract

Tobacco smoking is a major risk factor for cardiovascular disease and hypertension. It is associated with the oxidative stress and induces metabolic reprogramming, altering mitochondrial function. We hypothesized that cigarette smoke induces cardiovascular mitochondrial oxidative stress, which contributes to endothelial dysfunction and hypertension. To test this hypothesis, we studied whether the scavenging of mitochondrial H2O2 in transgenic mice expressing mitochondria-targeted catalase (mCAT) attenuates the development of cigarette smoke/angiotensin II-induced mitochondrial oxidative stress and hypertension compared with wild-type mice. Two weeks of exposure of wild-type mice with cigarette smoke increased systolic blood pressure by 17 mmHg, which was similar to the effect of a subpresssor dose of angiotensin II (0.2 mg·kg−1·day−1), leading to a moderate increase to the prehypertensive level. Cigarette smoke exposure and a low dose of angiotensin II cooperatively induced severe hypertension in wild-type mice, but the scavenging of mitochondrial H2O2 in mCAT mice completely prevented the development of hypertension. Cigarette smoke and angiotensin II cooperatively induced oxidation of cardiolipin (a specific biomarker of mitochondrial oxidative stress) in wild-type mice, which was abolished in mCAT mice. Cigarette smoke and angiotensin II impaired endothelium-dependent relaxation and induced superoxide overproduction, which was diminished in mCAT mice. To mimic the tobacco smoke exposure, we used cigarette smoke condensate, which induced mitochondrial superoxide overproduction and reduced endothelial nitric oxide (a hallmark of endothelial dysfunction in hypertension). Western blot experiments indicated that tobacco smoke and angiotensin II reduce the mitochondrial deacetylase sirtuin-3 level and cause hyperacetylation of a key mitochondrial antioxidant, SOD2, which promotes mitochondrial oxidative stress. NEW & NOTEWORTHY This work demonstrates tobacco smoking-induced mitochondrial oxidative stress, which contributes to endothelial dysfunction and development of hypertension. We suggest that the targeting of mitochondrial oxidative stress can be beneficial for treatment of pathological conditions associated with tobacco smoking, such as endothelial dysfunction, hypertension, and cardiovascular diseases. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/mitochondrial-oxidative-stress-in-smoking-and-hypertension/ .

Comparative assessment of individual RONS in serum of smokers compared with non-smokers and their correlation with the lipid profile and antioxidant status

“…During this process, O 2 -• and H 2 O 2 are produced, and these species are converted through an iron-catalysed reaction into HO • radical, leading to biological damage. 12,44 The significant elevation of Hb concentration and its related markers that occurred in the smokers group in this study was consistent with other reports. 32,38 This elevation is best explained as a compensatory mechanism that increases Hb concentration because of a lack of oxygencarrying capacity in carboxy-Hb, which results from continuous exposure of the smoker to carbon monoxide that is generated in the cigarette burning process.…”

Proteomic identification of the proteins related to cigarette smoke-induced cardiac hypertrophy in spontaneously hypertensive rats

“…Previous experimental studies have demonstrated that cigarette smoking causes endothelial dysfunction and cardiac hypertrophy through cellular oxidative stress and decreased NO bioavailability 25 . Cigarette smoking is also known to induce mitochondrial oxidative stress, which contributes to the development of hypertension 17 . On the other hand, one previous study reported that CS can induce cardiac hypertrophy without any increase in blood pressure 14 .…”

“…Synergistic effect between elevated blood pressure and CS exposure has also been reported in epidemiological studies 16 . In addition, CS exposure has been shown to induce cardiovascular oxidative stress 17 .…”

Role of Mitophagy in Cardiovascular Disease

“…Complications of hypertension such as atherosclerosis, myocardial I/R injury and hypertrophy, and heart failure are closely associated with cardiomyocyte and endothelial mitochondrial dysfunction [131]. Insufficient energy supply, kinetic imbalance, oxidative damage, abnormal signal transduction, and mitochondrial dysfunction caused by genetic mutations are risk factors for hypertension [132][133][134]. Myocardial hypertrophy associated with hypertension reportedly altered cardiomyocyte phenotype, function, and energy metabolism.…”