Molecular Mechanism Underlying Role of the XBP1s in Cardiovascular Diseases

Abstract

Spliced X-box binding protein-1 (XBP1s) is a protein that belongs to the cAMP-response element-binding (CREB)/activating transcription factor (ATF) b-ZIP family with a basic-region leucine zipper (bZIP). There is mounting evidence to suggest that XBP1s performs a critical function in a range of different cardiovascular diseases (CVDs), indicating that it is necessary to gain a comprehensive knowledge of the processes involved in XBP1s in various disorders to make progress in research and clinical therapy. In this research, we provide a summary of the functions that XBP1s performs in the onset and advancement of CVDs such as atherosclerosis, hypertension, cardiac hypertrophy, and heart failure. Furthermore, we discuss XBP1s as a novel therapeutic target for CVDs.

Novel Targets Regulating the Role of Endothelial Cells and Angiogenesis after Infarction: A RNA Sequencing Analysis

“…Our findings point to an overrepresentation of xbp1, a transcription factor that modulates not only the cellular response to endoplasmic reticulum stress, but also vascular endothelial growth factor-induced angiogenesis in adult tissues submitted to ischemia [37]. Despite its role in the mechanisms underlying various cardiovascular diseases, including cardiac hypertrophy and heart failure [37], few studies have addressed the involvement of xbp1 in the MI context.…”

Endoplasmic Reticulum Stress and Its Impact on Adipogenesis: Molecular Mechanisms Implicated

“…XBP1s, once activated, functions as a transcription factor that regulates the expression of different genes. Specifically, XBP1s promotes the expression of ERAD genes which facilitate the elimination of unnecessary misfolded proteins [85]. When specifically deleting the XBP1 gene in the adult mouse liver to investigate its function, we observed a significant reduction of approximately 85-90% in hepatic fatty acid and cholesterol synthesis.…”

XBP1 Modulates the Aging Cardiorenal System by Regulating Oxidative Stress

“…Furthermore, research has shown that the incidence of acute kidney injury (AKI) is higher in older adults [4]. The progression of kidney damage leads to an expansion of blood volume, along with an upregulation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS); these changes exert numerous maladaptive systemic effects on the heart, vasculature, and kidneys [5][6][7][8]. Compared to young hearts, aged hearts are more susceptible to both acute and chronic damage [9].…”

“…Aging is highly correlated to the process of mitochondrial dysfunction and causes the accumulation of oxidative stress in cardiomyocytes and nephrocytes [17,20,21]. Furthermore, oxidative stress participates in the generation of biomarkers that can be used to detect cardiorenal aging and functional deterioration, including brain natriuretic peptide (BNP)/N-terminal (NT)-pro hormone BNP (NT-proBNP), interleukin-1β (IL-1β), nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX), NLR family pyrin domain containing 3 (NLRP3) and neutrophil gelatinase associated lipocalin (NGAL) [7,22]. In addition to stimulating SNS and RAAS, oxidative stress weakens cardiorenal function by attenuating the restoration of mitochondrial health, alleviating mitochondrial biogenesis, enhancing proinflammatory and profibrotic pathways, and damaging the integrity and viability of cells and organs [6][7][8] (Figure 1).…”

“…Furthermore, oxidative stress participates in the generation of biomarkers that can be used to detect cardiorenal aging and functional deterioration, including brain natriuretic peptide (BNP)/N-terminal (NT)-pro hormone BNP (NT-proBNP), interleukin-1β (IL-1β), nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX), NLR family pyrin domain containing 3 (NLRP3) and neutrophil gelatinase associated lipocalin (NGAL) [7,22]. In addition to stimulating SNS and RAAS, oxidative stress weakens cardiorenal function by attenuating the restoration of mitochondrial health, alleviating mitochondrial biogenesis, enhancing proinflammatory and profibrotic pathways, and damaging the integrity and viability of cells and organs [6][7][8] (Figure 1). Cardiorenal abnormalities contribute to the accumulation of misfolded or unfolded proteins in the endoplasmic reticulum (ER), thereby exerting significant load on the ER protein-folding mechanism; this can overwhelm the capacity of the ER, a disease state known as ER stress [23,24].…”