Editorial

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Open AccessEditorial

Editorial for the Molecular Genetics and Genomics of Metabolic Disorders in Cardiovascular and Cerebrovascular Diseases Special Issue: June 2023

by Yuanyuan Zhao and Xin Tu

Genes 2023, 14(8), 1568; https://0-doi-org.brum.beds.ac.uk/10.3390/genes14081568 - 01 Aug 2023

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Abstract

Cardiovascular and cerebrovascular diseases are the leading causes of the mortality of humans in the 21st century [...] Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Metabolic Disorders in Cardiovascular and Cerebrovascular Diseases)

Research

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10 pages, 1322 KiB

Open AccessArticle

Polymorphic Variants of AGT, ABCA1, and CYBA Genes Influence the Survival of Patients with Coronary Artery Disease: A Prospective Cohort Study

by Anna Balcerzyk-Matić, Tomasz Nowak, Katarzyna Mizia-Stec, Joanna Iwanicka, Tomasz Iwanicki, Paweł Bańka, Alicja Jarosz, Artur Filipecki, Iwona Żak, Jolanta Krauze and Paweł Niemiec

Genes 2022, 13(11), 2148; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13112148 - 18 Nov 2022

Cited by 2 | Viewed by 1087

Abstract

Genetic factors can influence the risk of coronary artery disease (CAD) and the survival of patients. Our previous research led to the identification of genetic variants predisposing to CAD in the Polish population. Since many of them affect the clinical phenotype of the [...] Read more.

Genetic factors can influence the risk of coronary artery disease (CAD) and the survival of patients. Our previous research led to the identification of genetic variants predisposing to CAD in the Polish population. Since many of them affect the clinical phenotype of the disease, the aim of this study was searching for genetic factors potentially influencing survival in patients with CAD. The study included 276 patients hospitalized due to coronary artery disease. The database of medical history and genotypic results of 29 polymorphisms were used. The endpoint was defined as death from cardiovascular causes. Survival was defined as the period from angiographic confirmation of CAD to death from cardiovascular causes. Three of all the analyzed genes were associated with survival. In the case of the AGT (rs699) and ABCA1 (rs2230806) genes polymorphisms, the risk of death was higher in GG homozygotes compared to the A allele carriers in the 10-year period. In the case of the CYBA (rs72811418) gene polymorphism, the effect on mortality was shown in both 5- and 10-year periods. The TA heterozygotes were predisposed to a higher risk of death than the TT homozygotes. Concluding, the AGT, ABCA1, and CYBA genes polymorphisms influence the risk of death in patients with CAD. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Metabolic Disorders in Cardiovascular and Cerebrovascular Diseases)

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10 pages, 3180 KiB

Open AccessArticle

FBN1 Splice-Altering Mutations in Marfan Syndrome: A Case Report and Literature Review

by James Jiqi Wang, Bo Yu, Yang Sun, Xiuli Song, Dao Wen Wang and Zongzhe Li

Genes 2022, 13(10), 1842; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13101842 - 12 Oct 2022

Cited by 3 | Viewed by 2323

Abstract

Marfan syndrome (MFS) is a life-threatening autosomal dominant genetic disorder of connective tissue caused by the pathogenic mutation of FBN1. Whole exome sequencing and Sanger sequencing were performed to identify the pathogenic mutation. The transcriptional consequence of the splice-altering mutation was analyzed [...] Read more.

Marfan syndrome (MFS) is a life-threatening autosomal dominant genetic disorder of connective tissue caused by the pathogenic mutation of FBN1. Whole exome sequencing and Sanger sequencing were performed to identify the pathogenic mutation. The transcriptional consequence of the splice-altering mutation was analyzed via minigene assays and reverse-transcription PCR. We identified a novel pathogenic mutation (c.8051+1G>C) in the splice site of exon 64 of the FBN1 gene in an MFS-pedigree. This mutation was confirmed to cause two different truncated transcripts (entire exon 64 skipping; partial exon 64 exclusion). We also systematically summarized previously reported transcriptional studies of pathogenic splice-altering mutations in the FBN1 gene to investigate the clinical and transcriptional consequences. In conclusion, we reported for the first time that a splice-altering mutation in the FBN1 gene leads to two abnormal transcripts simultaneously. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Metabolic Disorders in Cardiovascular and Cerebrovascular Diseases)

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17 pages, 7848 KiB

Open AccessArticle

BAG3 Alleviates Atherosclerosis by Inhibiting Endothelial-to-Mesenchymal Transition via Autophagy Activation

by Hongtao Diao, Kaili Wu, Dingming Lan, Dongwei Wang, Jingjing Zhao, Bingying Huang, Xiaoqi Shao, Ruonan Wang, Huiling Tan, Xinyuan Tang, Meiling Yan and Yue Zhang

Genes 2022, 13(8), 1338; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13081338 - 26 Jul 2022

Cited by 6 | Viewed by 2200

Abstract

Atherosclerosis is a chronic systemic inflammatory disease that causes severe cardiovascular events. B cell lymphoma 2-associated athanogene (BAG3) was proven to participate in the regulation of tumor angiogenesis, neurodegenerative diseases, and cardiac diseases, but its role in atherosclerosis remains unclear. Here, we aim [...] Read more.

Atherosclerosis is a chronic systemic inflammatory disease that causes severe cardiovascular events. B cell lymphoma 2-associated athanogene (BAG3) was proven to participate in the regulation of tumor angiogenesis, neurodegenerative diseases, and cardiac diseases, but its role in atherosclerosis remains unclear. Here, we aim to investigate the role of BAG3 in atherosclerosis and elucidate the potential molecular mechanism. In this study, ApoE^−/− mice were given a tail-vein injection of BAG3-overexpressing lentivirus and fed a 12-week high-fat diet (HFD) to investigate the role of BAG3 in atherosclerosis. The overexpression of BAG3 reduced plaque areas and improved atherosclerosis in ApoE^−/− mice. Our research proves that BAG3 promotes autophagy in vitro, contributing to the suppression of EndMT in human umbilical vein endothelial cells (HUVECs). Mechanically, autophagy activation is mediated by BAG3 via the interaction between BAG3 and its chaperones HSP70 and HSPB8. In conclusion, BAG3 facilitates autophagy activation via the formation of the chaperone-assisted selective autophagy (CASA) complex interacting with HSP70 and HSPB8, leading to the inhibition of EndMT during the progression of atherosclerosis and indicating that BAG3 is a potential therapeutic target for atherosclerosis. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Metabolic Disorders in Cardiovascular and Cerebrovascular Diseases)

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16 pages, 3863 KiB

Open AccessArticle

The Effect of Angiotensin Converting Enzyme (ACE) I/D Polymorphism on Atherosclerotic Cardiovascular Disease and Cardiovascular Mortality Risk in Non-Hemodialyzed Chronic Kidney Disease: The Mediating Role of Plasma ACE Level

by Hendri Susilo, Budi Susetyo Pikir, Mochammad Thaha, Mochamad Yusuf Alsagaff, Satriyo Dwi Suryantoro, Citrawati Dyah Kencono Wungu, Ifan Ali Wafa, Cennikon Pakpahan and Delvac Oceandy

Genes 2022, 13(7), 1121; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13071121 - 23 Jun 2022

Cited by 6 | Viewed by 2883

Abstract

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the [...] Read more.

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the association between ACE I/D polymorphism and cardiovascular mortality risk among non-hemodialyzed chronic kidney disease patients. This cross-sectional study examined 70 patients of Javanese ethnic origin with stable CKD who did not receive hemodialysis. ACE I/D polymorphisms, plasma ACE levels, atherosclerotic cardiovascular disease (ASCVD) risk, and cardiovascular mortality risk were investigated. As per our findings, the I allele was found to be more frequent (78.6) than the D allele (21.4), and the DD genotype was less frequent than the II genotype (4.3 vs. 61.4). The ACE I/D polymorphism had a significant direct positive effect on plasma ACE levels (path coefficient = 0.302, p = 0.021). Similarly, plasma ACE levels had a direct and significant positive effect on the risk of atherosclerotic cardiovascular disease (path coefficient = 0.410, p = 0.000). Moreover, atherosclerotic cardiovascular disease risk had a significant positive effect on cardiovascular mortality risk (path coefficient = 0.918, p = 0.000). The ACE I/D polymorphism had no direct effect on ASCVD and cardiovascular mortality risk. However, our findings show that the indirect effects of high plasma ACE levels may be a factor in the increased risk of ASCVD and cardiovascular mortality in Javanese CKD patients. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Metabolic Disorders in Cardiovascular and Cerebrovascular Diseases)

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15 pages, 2976 KiB

Open AccessArticle

MED12 Regulates Smooth Muscle Cell Functions and Participates in the Development of Aortic Dissection

by Yingchao Zhou, Lingfeng Zha, Jianfei Wu, Mengru Wang, Mengchen Zhou, Gang Wu, Xiang Cheng, Zhengrong Huang, Qiang Xie and Xin Tu

Genes 2022, 13(4), 692; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13040692 - 14 Apr 2022

Cited by 2 | Viewed by 2255

Abstract

Aortic dissection (AD) is a life-threatening disease with high morbidity and mortality, and effective pharmacotherapeutic remedies for it are lacking. Therefore, AD’s molecular pathogenesis and etiology must be elucidated. The aim of this study was to investigate the possible mechanism of mediator complex [...] Read more.

Aortic dissection (AD) is a life-threatening disease with high morbidity and mortality, and effective pharmacotherapeutic remedies for it are lacking. Therefore, AD’s molecular pathogenesis and etiology must be elucidated. The aim of this study was to investigate the possible mechanism of mediator complex subunit 12 (human: MED12, mouse: Med12)involvement in AD. Firstly, we examined the expression of MED12 protein (human: MED12, mouse: Med12) in the aortic tissues of AD patients and AD mice. Subsequently, Med12 gene silencing was accomplished with RNA interference (siRNA). The effects of Med12 on AD and the possible biological mechanisms were investigated based on the proliferation, senescence, phenotypic transformation, and its involved signal pathway of mouse aortic smooth muscle cells (MOVAS), s. The results show that the expression of MED12 in the aortae of AD patients and AD mice was decreased. Moreover, the downregulation of Med12 inhibited the proliferation of MOVAS and promoted senescence. Further research found that Med12, as an inhibitor of the TGFβ1 signaling pathway, reduced the expression of Med12 and enhanced the activity of the TGFβ1 nonclassical signaling pathway, while TGFβ1 inhibited the phenotype transformation and proliferation of MOVAS by inhibiting Med12 synthesis. In conclusion, Med12 affected the phenotype, proliferation, and senescence of MOVAS through the TGFβ signaling pathway. This study provides a potential new target for the prevention and treatment of AD. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Metabolic Disorders in Cardiovascular and Cerebrovascular Diseases)

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23 pages, 27777 KiB

Open AccessArticle

Quantitative Real-Time Analysis of Differentially Expressed Genes in Peripheral Blood Samples of Hypertension Patients

by Fawad Ali, Arifullah Khan, Syed Aun Muhammad and Syed Shams ul Hassan

Genes 2022, 13(2), 187; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13020187 - 21 Jan 2022

Cited by 12 | Viewed by 3910

Abstract

Hypertension (HTN) is considered one of the most important and well-established reasons for cardiovascular abnormalities, strokes, and premature mortality globally. This study was designed to explore possible differentially expressed genes (DEGs) that contribute to the pathophysiology of hypertension. To identify the DEGs of [...] Read more.

Hypertension (HTN) is considered one of the most important and well-established reasons for cardiovascular abnormalities, strokes, and premature mortality globally. This study was designed to explore possible differentially expressed genes (DEGs) that contribute to the pathophysiology of hypertension. To identify the DEGs of HTN, we investigated 22 publicly available cDNA Affymetrix datasets using an integrated system-level framework. Gene Ontology (GO), pathway enrichment, and transcriptional factors were analyzed to reveal biological information. From 50 DEGs, we ranked 7 hypertension-related genes (p-value < 0.05): ADM, ANGPTL4, USP8, EDN, NFIL3, MSR1, and CEBPD. The enriched terms revealed significant functional roles of HIF-1-α transcription; endothelin; GPCR-binding ligand; and signaling pathways of EGF, PIk3, and ARF6. SP1 (66.7%), KLF7 (33.3%), and STAT1 (16.7%) are transcriptional factors associated with the regulatory mechanism. The expression profiles of these DEGs as verified by qPCR showed 3-times higher fold changes (2−ΔΔCt) in ADM, ANGPTL4, USP8, and EDN1 genes compared to control, while CEBPD, MSR1 and NFIL3 were downregulated. The aberrant expression of these genes is associated with the pathophysiological development and cardiovascular abnormalities. This study will help to modulate the therapeutic strategies of hypertension. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Metabolic Disorders in Cardiovascular and Cerebrovascular Diseases)

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13 pages, 4080 KiB

Open AccessArticle

Causal Association between Periodontal Diseases and Cardiovascular Diseases

by Mengchen Zhou, Jiangtao Dong, Lingfeng Zha and Yuhua Liao

Genes 2022, 13(1), 13; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13010013 - 22 Dec 2021

Cited by 14 | Viewed by 5065

Abstract

Observational studies have revealed that dental diseases such as periodontitis and dental caries increase the risk of cardiovascular diseases (CVDs). However, the causality between periodontal disease (PD) and CVDs is still not clarified. In the present study, two-sample Mendelian randomization (MR) studies were [...] Read more.

Observational studies have revealed that dental diseases such as periodontitis and dental caries increase the risk of cardiovascular diseases (CVDs). However, the causality between periodontal disease (PD) and CVDs is still not clarified. In the present study, two-sample Mendelian randomization (MR) studies were carried out to assess the association between genetic liability for periodontal diseases (dental caries and periodontitis) and major CVDs, including coronary artery disease (CAD), heart failure (HF), atrial fibrillation (AF), and stroke—including ischemic stroke as well as its three main subtypes—based on large-scale genome-wide association studies (GWASs). Our two-sample MR analyses did not provide evidence for dental caries and periodontitis as the causes of cardiovascular diseases; sensitivity analyses, including MR–Egger analysis and weighted median analysis, also supported this result. Gene functional annotation and pathway enrichment analyses indicated the common pathophysiology between cardiovascular diseases and periodontal diseases. The associations from observational studies may be explained by shared risk factors and comorbidities instead of direct consequences. This also suggests that addressing the common risk factors—such as reducing obesity and improving glucose tolerance—could benefit both conditions. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Metabolic Disorders in Cardiovascular and Cerebrovascular Diseases)

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Review

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10 pages, 262 KiB

Open AccessReview

Twenty-Five Years of Contemplating Genotype-Based Hereditary Hemochromatosis Population Screening

by Jörg Schmidtke

Genes 2022, 13(9), 1622; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13091622 - 09 Sep 2022

Cited by 6 | Viewed by 1625

Abstract

Hereditary hemochromatosis (HH) is a rather frequent, preventable disease because the progressive iron overload affecting many organs can be effectively reduced by phlebotomy. Even before the discovery of the major gene, HFE, in 1996, hemochromatosis was seen as a candidate for population-wide [...] Read more.

Hereditary hemochromatosis (HH) is a rather frequent, preventable disease because the progressive iron overload affecting many organs can be effectively reduced by phlebotomy. Even before the discovery of the major gene, HFE, in 1996, hemochromatosis was seen as a candidate for population-wide screening programmes. A US Centers of Disease Control and the National Human Genome Research Institute expert panel convened in 1997 to consider genotype-based HH population-wide screening and decided that the scientific evidence available at that time was insufficient and advised against. In spite of a large number of studies performed within the last 25 years, addressing all aspects of HH natural history, health economics, and social acceptability, no professional body worldwide has reverted this decision, and HH remains a life-threatening condition that often goes undetected at a curable stage. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Metabolic Disorders in Cardiovascular and Cerebrovascular Diseases)

16 pages, 1817 KiB

Open AccessReview

New Insights into the Functions of MicroRNAs in Cardiac Fibrosis: From Mechanisms to Therapeutic Strategies

by Yuanyuan Zhao, Dunfeng Du, Shanshan Chen, Zhishui Chen and Jiajia Zhao

Genes 2022, 13(8), 1390; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13081390 - 04 Aug 2022

Cited by 15 | Viewed by 2318

Abstract

Cardiac fibrosis is a significant global health problem associated with almost all types of heart disease. Extensive cardiac fibrosis reduces tissue compliance and contributes to adverse outcomes, such as cardiomyocyte hypertrophy, cardiomyocyte apoptosis, and even heart failure. It is mainly associated with pathological [...] Read more.

Cardiac fibrosis is a significant global health problem associated with almost all types of heart disease. Extensive cardiac fibrosis reduces tissue compliance and contributes to adverse outcomes, such as cardiomyocyte hypertrophy, cardiomyocyte apoptosis, and even heart failure. It is mainly associated with pathological myocardial remodeling, characterized by the excessive deposition of extracellular matrix (ECM) proteins in cardiac parenchymal tissues. In recent years, a growing body of evidence demonstrated that microRNAs (miRNAs) have a crucial role in the pathological development of cardiac fibrosis. More than sixty miRNAs have been associated with the progression of cardiac fibrosis. In this review, we summarized potential miRNAs and miRNAs-related regulatory mechanisms for cardiac fibrosis and discussed the potential clinical application of miRNAs in cardiac fibrosis. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Metabolic Disorders in Cardiovascular and Cerebrovascular Diseases)

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