Atherosclerosis susceptible genes

Manganese (Mn) is an essential trace element with unique functions in the body; it acts as a cofactor for many enzymes involved in energy metabolism, the endogenous antioxidant enzyme systems, neurotransmitter production, and the regulation of reproductive hormones. However, overexposure to Mn is toxic, particularly to the central nervous system (CNS) due to it causing the progressive destruction of nerve cells. Exposure to manganese is widespread and occurs by inhalation, ingestion, or dermal contact. Associations have been observed between Mn accumulation and neurodegenerative diseases such as manganism, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis...

The steroid 11beta-hydroxylase inhibitor metyrapone is able to effectively reverse the hypercortisolemia detected in human Cushing's Syndrome patients. In this current preclinical study, we investigated whether metyrapone monotherapy can also reverse the hypercortisolemia-associated increase in atherosclerotic cardiovascular disease risk. In this instance, female low-density lipoprotein receptor knockout mice fed a cholic acid-containing high cholesterol/high fat diet to induce the development of hypercorticosteronemia and atherosclerotic lesions were treated twice daily with 100 mg/kg metyrapone for 4 weeks...

Atherosclerosis is a progressive, degenerative vascular disease and a leading cause of morbidity and mortality. In response to endothelial damage, platelet derived growth factor (PDGF)-BB induced phenotypic modulation of medial smooth muscle cells (VSMCs) promotes atherosclerotic lesion formation and destabilisation of the vessel wall. VSMC sensitivity to PDGF-BB is determined by endocytosis of Low density lipoprotein receptor related protein 1 (LRP1)-PDGFR β complexes to balance receptor recycling with lysosomal degradation...

BACKGROUND AND AIMS: RNF213 is a susceptibility gene for moyamoya disease and vasospastic angina, with a second hit considered necessary for their development. Elevated thyroid peroxidase antibody (TPO-Ab) levels have been observed in both diseases, suggesting a possible role of TPO-Ab as a second hit for developing RNF213-related vasculopathy. We investigated the association of TPO-Ab levels with RNF213-related ischemic stroke (IS)/transient ischemic attack (TIA), other than moyamoya disease...

Corona virus disease 2019 (COVID-19) is prone to induce multiple organ damage. The kidney is one of the target organs of SARS-CoV-2, which is susceptible to inducing acute kidney injury (AKI). Huanglian Jiedu Decoction (HLJDD) is one of the recommended prescriptions for COVID-19 with severe complications. We used network pharmacology and molecular docking to explore the therapeutic and protective effects of HLJDD on COVID-19-associated AKI. Potential targets related to "HLJDD," "COVID-19," and "Acute Kidney Injury/Acute Renal Failure" were identified from several databases...

COVID-19 is a severe respiratory disease caused by SARS-CoV-2, a novel human coronavirus. Patients infected with SARS-CoV-2 exhibit heterogeneous symptoms that pose pragmatic hurdles for implementing appropriate therapy and management of the COVID-19 patients and their post-COVID complications. Thus, understanding the impact of infection severity at the molecular level in the host is vital to understand the host response and accordingly it's precise management. In the current study, we performed a comparative transcriptomics analysis of publicly available seven asymptomatic and eight severe COVID-19 patients...

BACKGROUND: Plasma amyloid-β (Aβ) (Aβ42 , Aβ40 , and Aβ42 /Aβ40 ), biomarkers of the Alzheimer's form of dementia, are under consideration for clinical use. The associations of these peptides with circulating proteins may identify novel plasma biomarkers of dementia and inform peripheral factors influencing the levels of these peptides. METHODS: We analyzed the association of these 3 plasma Aβ measures with 4638 circulating proteins among a subset of the participants of the Atherosclerosis Risk in Communities (ARIC) study (midlife: n  = 1955; late life: n  = 2082), related the Aβ-associated proteins with incident dementia in the overall ARIC cohort (midlife: n  = 11,069, late life: n  = 4110) with external replication in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study ( n  = 4973), estimated the proportion of Aβ variance explained, and conducted enrichment analyses to characterize the proteins associated with the plasma Aβ peptides...

BACKGROUND: Atherosclerotic plaques are complex tissues composed of a heterogeneous mixture of cells. However, we have limited understanding of the comprehensive transcriptional and phenotypical landscape of the cells within these lesions. METHODS: To characterize the landscape of human carotid atherosclerosis in greater detail, we combined cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell RNA sequencing (scRNA-seq) to classify all cell types within lesions (n=21; 13 symptomatic) to achieve a comprehensive multimodal understanding of the cellular identities of atherosclerosis and their association with clinical pathophysiology...

AIM: To investigate individual susceptibility to periodontitis by conducting an epigenome-wide association study using peripheral blood. MATERIALS AND METHODS: We included 1077 African American and 457 European American participants of the Atherosclerosis Risk in Communities (ARIC) study who had completed a dental examination or reported being edentulous at Visit 4 and had available data on DNA methylation from Visit 2 or 3. DNA methylation levels were compared by periodontal disease severity and edentulism through discovery analyses and subsequent testing of individual CpGs...

INTRODUCTION AND OBJECTIVES: Transcription factor 21 (TCF21) is a member of the basic helix-loop-helix (bHLH) transcription factor family, and is critical for embryogenesis of the heart. It regulates differentiation of epicardium-derived cells into smooth muscle cell (SMC) and fibroblast lineages. The biological role of TCF21 in the progression of atherosclerosis is the subject of debate. The aim of this study was to investigate the impact of the TCF21 rs12190287 gene variant on the prognosis of coronary artery disease (CAD) in a Portuguese population from Madeira island...

BACKGROUND: Coronary artery disease (CAD) is a multi-factor complex trait and is heritable, especially in early-onset families. However, the genetic factors affecting the susceptibility of early-onset CAD are not fully characterized. METHODS: In the present study, we identified a rare nonsense variant in the CYP17A1 gene from a Chinese Han family with CAD. To validate the effect of this variation on atherosclerosis and early-onset coronary artery disease, we conducted studies on population, cells, and mice...

BACKGROUND: Genetic risk factors substantially contributed to the development of coronary atherosclerosis. Genome-wide association study (GWAS) has identified many risk loci for coronary atherosclerosis, but the translation of these loci into therapeutic targets is limited for their location in non-coding regions. Here, we aimed to screen the potential coronary atherosclerosis pathogenic genes expressed though TWAS (transcriptome wide association study) and explore the underlying mechanism association...

Atherogenesis is an insipidus but precipitating process leading to serious consequences of many cardiovascular diseases (CVD). Numerous genetic loci contributing to atherosclerosis have been identified in human genome-wide association studies, but these studies have limitations in the ability to control environmental factors and to decipher cause/effect relationships. To assess the power of hyperlipidemic Diversity Outbred (DO) mice in facilitating quantitative trait loci (QTL) analysis of complex traits, we generated a high-resolution genetic panel of atherosclerosis susceptible (DO-F1) mouse cohort by crossing 200 DO females with C57BL/6J males carrying two human genes: encoding apolipoprotein E3-Leiden and cholesterol ester transfer protein...

Stroke is a key cerebrovascular disease and important cause of death and disability worldwide, including in the kingdom of Saudi Arabia (KSA). It has a large economic burden and serious socioeconomic impacts on patients, their families and the community. The incidence of ischemic stroke is probably increased by the interaction of GSTT1 and GSTM1 null genotypes with high blood pressure, diabetes and cigarette smoking. The roles of VWF, GSTs and TNF-alpha gene variations in the induction of stroke are still uncertain and require further examination...

The fat mass and obesity-associated ( FTO ) gene was the first obesity-susceptibility gene identified through a genome-wide association study (GWAS). A growing number of studies have suggested that genetic variants of FTO are strongly associated with the risk of cardiovascular diseases, including hypertension and acute coronary syndrome. In addition, FTO was also the first N6 -methyladenosine (m6A) demethylase, suggesting the reversible nature of m6A modification. m6A is dynamically deposited, removed, and recognized by m6A methylases, demethylases, and m6A binding proteins, respectively...

BACKGROUND: Genetic variants at the TRIB1 gene locus are strongly associated with plasma lipid traits and the risk of coronary artery disease in humans. Here, we analyzed the consequences of Trib1 deficiency on lipid metabolism and atherosclerotic lesion formation in atherosclerosis-susceptible Ldlr -/ - . METHODS: Trib1 -/- mice were crossed onto the Ldlr -/- background to generate double-knockout mice ( Trib1 -/- Ldlr -/- ) and fed a semisynthetic, modified AIN76 diet (0...

Hypoxia in the neonatal period is associated with early manifestations of adverse cardiovascular health in adulthood including higher risk of hypertension and atherosclerosis. We hypothesize that this occurs due to activation of lysyl oxidases (LOXs) and the remodeling of the large conduit vessels, leading to early arterial stiffening. Newborn C57Bl/6 mice were exposed to hypoxia (FiO2  = 11.5%) from postnatal day 1 (P1) to postnatal day 11 (P11), followed by resumption of normoxia. Controls were maintained in normoxia...

Protein arginine methyltransferase 5 (PRMT5) controls inflammation and metabolism through modulation of histone methylation and gene transcription. Given the important role of inflammation and metabolism in atherosclerotic cardiovascular disease, here we examined the role of PRMT5 in atherosclerosis using the specific PRMT5 inhibitor GSK3326595. Cultured thioglycollate-elicited peritoneal macrophages were exposed to GSK3326595 or DMSO control and stimulated with either 1 ng/mL LPS or 100 ng/mL interferon-gamma for 24 h...

Paraoxonase 1 (PON1), residing almost exclusively on HDL, was discovered because of its hydrolytic activity towards organophosphates. Subsequently, it was also found to hydrolyse a wide range of substrates, including lactones and lipid hydroperoxides. PON1 is critical for the capacity of HDL to protect LDL and outer cell membranes against harmful oxidative modification, but this activity depends on its location within the hydrophobic lipid domains of HDL. It does not prevent conjugated diene formation, but directs lipid peroxidation products derived from these to become harmless carboxylic acids rather than aldehydes which might adduct to apolipoprotein B...

Metabolic syndrome (MetS) is one of the most important health issues around the world and a major risk factor for both type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The etiology of MetS is determined by the interaction between genetic and environmental factors. Effective prevention and treatment of MetS notably decreases the risk of its complications such as diabetes, obesity, hypertension, and dyslipidemia. According to recent genome-wide association studies, multiple genes are involved in the incidence and development of MetS...