Increased plasma sestrin2 concentrations in patients with chronic heart failure and predicted the occurrence of major adverse cardiac events: A 36-month follow-up cohort study
Introduction
Numerous basic heart diseases, including abnormal heart structure and coronary artery disease, could result in the occurrence of chronic heart failure (CHF), which could further lead to the decline in activity tolerance and a variety of serious clinical complications. Among them, cardiac events are the most serious complications of CHF, many patients lose their lives without even having access to treatment [[1], [2], [3]]. Therefore, it is necessary to find some markers to predict the occurrence of cardiac events.
A total of 3 Sestrins (Sesns) members were discovered according to previous studies, including Sesn1, Sesn2, and Sesn3 [[4], [5], [6]]. Among them, Sesn2 is an important stress-induced protein and widely expressed in mammals [4,5]. Sesn2 could be secreted by numerous non-immune cells and immune cells, and the main sources are macrophages and T lymphocytes [7,8]. A variety of environmental stresses could promote Sesn2 secretion, the most important role should be stimulated by oxidative stress and the Sesn2 concentrations even indirectly reflect oxidative stress concentrations [6,9]. Sesn2 was also found to participated in diseases of multiple systems and play a protective role without exception via regulating apoptosis, toxicity, and oxidative stress [[10], [11], [12], [13]].
Recent research also suggested that Sese2 was closely related to the progression and development of cardiovascular diseases via maintain the balance of oxidative stress, such as hypertension, cardiac ischemia reperfusion injury, cardiac fibrosis, and atrial fibrillation [[14], [15], [16], [17]]. In addition, plasma Sesn2 concentrations were observed to increase in patients with coronary artery diseases, and positively correlated with Gensini score and oxidative stress concentrations [18]. Furthermore, increased Sesn2 expression was observed in human failing hearts and positively correlated with heart BNP and collagen concentrations [19]. However, the circulating Sesn2 concentrations in CHF patients and the role between Sesn2 concentrations and the occurrence of cardiac evens remains unknown.
Section snippets
Study population
The present study was a retrospective cohort study. Individuals (n = 80) who received a health check-up at the medical center and had been ruled out significant heart disease were enrolled as control subjects in this study, the significant heart diseases including coronary artery disease (CAD), systolic and diastolic dysfunction, valvular heart disease, or myocardial hypertrophy on echocardiography. Consecutive patients (n = 220) who were admitted for the treatment of worsening CHF, diagnosis
Comparison of clinical characteristics between control and CHF groups
The data of clinical characteristics were obtained from echocardiography results, laboratory results, and clinical course records. Importantly, increased age, heart rate (HR), fasting glucose (Glu), creatinine (CREA), C-reactive protein (CRP), N-terminal B-type natriuretic peptide (NT-pro BNP), and LV end-diastolic dimension (LVEDD) and reduced body mass index (BMI), total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), albumin, and LVEF were found in CHF group when compared to
Discussion
We found that the circulating Sesn2 concentrations were increased in the CHF patients, the NYHA classification, rather than the etiologies of CHF, could affect the plasma Sesn2 concentrations. In addition, the Sensn2 concentrations were positively correlated with NT-proBNP concentrations, but negatively correlated with LVEF in CHF patients. Furthermore, Sesn2 were significantly increased in CHF patients with major adverse cardiac events when compared with CHF patients without major adverse
References (35)
- et al.
Association of platelet-derived growth factor receptor β accumulation with increased oxidative stress and cellular injury in sestrin 2 silenced human glioblastoma cells
FEBS Lett.
(2011) - et al.
p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling
Cell
(2008) - et al.
SESN-1 is a positive regulator of lifespan in Caenorhabditis elegans
Exp. Gerontol.
(2013) - et al.
Sestrins increase in patients with coronary artery disease and associate with the severity of coronary stenosis
Clin. Chim. Acta
(2017) - et al.
Sestrins increase in patients with coronary artery disease and associate with the severity of coronary stenosis
Clin. Chim. Acta
(2017) - et al.
AMPK/PGC1α activation by melatonin attenuates acute doxorubicin cardiotoxicity via alleviating mitochondrial oxidative damage and apoptosis
Free Radic. Biol. Med.
(2018) - et al.
Heart failure
New Engl J Med
(2003) - et al.
Signaling effectors underlying pathologic growth and remodeling of the heart
J. Clin. Invest.
(2013) - et al.
Cardiac remodeling at the population concentration-risk factors, screening, and outcomes
Nat. Rev. Cardiol.
(2011) - et al.
Role of histone acetylation in the activity-dependent regulation of sulfiredoxin and sestrin 2
Epigenetics
(2009)
Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability
Oncogene
Upregulation of Sestrin2 expression protects against macrophage apoptosis induced by oxidized low-density lipoprotein
DNA Cell Biol.
Regulation of toll-like receptor-mediated Sestrin2 induction by AP-1, Nrf2, and the ubiquitin-proteasome system in macrophages
Toxicol. Sci.
Recent insights into the biological functions of Sestrins in health and disease
Cell. Physiol. Biochem.
Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species
Proc. Natl. Acad. Sci. U. S. A.
Sestrin2 decreases renal oxidative stress, lowers blood pressure, and mediates dopamine D2 receptor-induced inhibition of reactive oxygen species production
Hypertension
Sestrin2 decreases renal oxidative stress, lowers blood pressure, and mediates dopamine D2 receptor-induced inhibition of reactive oxygen species production
Hypertension
Cited by (24)
Utilizing shared frailty with the Cox proportional hazards regression: Post discharge survival analysis of CHF patients
2023, Journal of Biomedical InformaticsSestrin 2, a potential star of antioxidant stress in cardiovascular diseases
2021, Free Radical Biology and MedicineCitation Excerpt :These studies strongly suggest that Sesn2 may be a key molecular target for the treatment of cardiac remodeling. Recently, several clinical studies have shown that the circulating Sesn2 level positively correlates with blood pressure (including systolic and diastolic blood pressure) and the severity of chronic heart failure, suggesting that Sesn2 participates in hypertension and heart failure through regulating oxidative stress, which provides further evidence that Sesn2 participates in the regulation of oxidative stress in CVDs [173,174]. Oxidative stress has long been considered to be closely related to a variety of CVDs.
Sestrin2 maintains OXPHOS integrity to modulate cardiac substrate metabolism during ischemia and reperfusion
2021, Redox BiologyCitation Excerpt :Sesn2 is a stress inducible protein which was upregulated in response to various stimuli, such as hypoxia and oxidative stress [12]. Several clinical reports announced that the expression of Sesn2 in myocardium and in plasma was significantly up-regulated in chronic heart failure (CHF) patients and coronary artery disease (CAD) patients [36,37]. Furthermore, the high concentration of Sesn2 in plasma were positively correlated with the high risk of incidence of major adverse cardiac events.
Sestrin 2 controls the cardiovascular aging process via an integrated network of signaling pathways
2020, Ageing Research ReviewsCitation Excerpt :The prospect of using Sesn2 as a serum biomarker has recently gained prominence. In patients with coronary heart disease (CAD), aortic dissection (AD), and chronic heart failure (CHF), the level of Sesn2 increases and appears to be related to the severity of CAD and CHF (Wang et al., 2019a; Xiao et al., 2019b; Ye et al., 2017). In addition, major risk factors for CAD such as advanced age, obesity, and diabetes, all increase the level of plasma Sesn2, which may be related to the reduction of oxidative stress and further confirms the cardiovascular protective effects of Sesn2 (Xiao et al., 2019b; Ye et al., 2017).
Sestrin2 as a potential therapeutic target for cardiovascular diseases
2020, Pharmacological ResearchCitation Excerpt :Also, Golpour et al. have reported that plasma level of Sestrin2 has been shown in a trend of decrease in obesity and type 2 diabetes (T2DM) by targeting Nrf2 activation [123]. Wang and colleagues have measured 220 patients with chronic heart failure (CHF), and found that Sestrin2 concentrations is positively related to the N-terminal B-type natriuretic peptide (NT-pro BNP) but negatively correlated with left ventricular ejection fraction (LVEF) [100]. Furthermore, Sestrin2 may be a potential predicting major adverse cardiac events during CHF.
Plasma sestrin2 concentrations and carotid atherosclerosis
2020, Clinica Chimica ActaCitation Excerpt :Sestrin2 is a stress-inducible anti-oxidant protein that was originally identified as a hypoxia-induced gene 95 (Hi95) and was reported to be induced by various stress, such as hypoxia, DNA damage, and oxidative stress [1]. Sestrin2 could be expressed and secreted by numerous immune cells and non-immune cells, and the main sources of sestrin2 are macrophages, T lymphocytes, and endothelial cells [2–4]. Sestrin2 expression was reported to be induced by angiotensin II in human umbilical vein endothelial cells (HUVECs), and the knockdown of sestrin2 promoted angiotensin II-induced apoptosis and oxidative stress [5].