Osteopontin and LDLR Are Upregulated in Hearts of Sudden Cardiac Death Victims With Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus

Patel, Mausam; Rodriguez, Daniela; Yousefi, Keyvan; John-Williams, Krista; Mendez, Armando J.; Goldberg, Ronald; Lymperopoulos, Anastasios; Tamariz, Leonardo; Goldberger, Jeffrey J.; Myerburg, Robert J.; Junttila, Juhani

doi:10.3389/fcvm.2020.610282

Cited by 7 publications

(6 citation statements)

References 32 publications

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“…The vital roles of FN1 and POSTN in heart and kidney disease have previously been reported. discovered that the expression of FN1 increased in patients with sudden cardio death [46]. Cardiofibrosis has a significant influence on the prognosis of heart diseases, which can be regulated by POSTN [47,48].…”

Section: Discussionmentioning

confidence: 99%

“…The vital roles of FN1 and POSTN in heart and kidney disease have previously been reported. Wang et al found that FN1 was associated with immune infiltration in diabetic nephropathy [ 43 ], Su et al reported that FN1 could regulate the process of renal fibrosis [ 44 ], Zhao et al disclosed that FN1 was involved in rat H9C2 cardiomyocyte growth by regulating cell cycle arrest [ 45 ], and Patel et al discovered that the expression of FN1 increased in patients with sudden cardio death [ 46 ]. Cardiofibrosis has a significant influence on the prognosis of heart diseases, which can be regulated by POSTN [ 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

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Identification and external validation of the hub genes associated with cardiorenal syndrome through time-series and network analyses

Liang

Huang

et al. 2022

Aging

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Cardiorenal syndrome (CRS), defined as acute or chronic damage to the heart or kidney triggering impairment of another organ, has a poor prognosis. However, the molecular mechanisms underlying CRS remain largely unknown. The RNA-sequencing data of the left ventricle tissue isolated from the sham-operated and CRS model rats at different time points were downloaded from the Gene Expression Omnibus (GEO) database. Genomic differences, protein-protein interaction networks, and short time-series analyses, revealed fibronectin 1 (FN1) and periostin (POSTN) as hub genes associated with CRS progression. The transcriptome sequencing data of humans obtained from the GEO revealed that FN1 and POSTN were both significantly associated with many different heart and kidney diseases. Peripheral blood samples from 20 control and 20 CRS patients were collected from the local hospital, and the gene expression levels of FN1 and POSTN were detected by real-time quantitative polymerase chain reaction. FN1 (area under the curve [AUC] = 0.807) and POSTN (AUC = 0.767) could distinguish CRS in the local cohort with high efficacy and were positively correlated with renal and heart damage markers, such as left ventricular ejection fraction. To improve the diagnostic ability, diagnosis models comprising FN1 and POSTN were constructed by logistic regression (F-Score = 0.718), classification tree (F-Score = 0.812), and random forest (F-Score = 1.000). Overall, the transcriptome data of CRS rat models were systematically analyzed, revealing that FN1 and POSTN were hub genes, which were validated in different public datasets and the local cohort.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification and external validation of the hub genes associated with cardiorenal syndrome through time-series and network analyses

Liang

Huang

et al. 2022

Aging

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“…In people with SCD, type 2 diabetes mellitus, and preserved ejection fraction, the expression of the FN1 gene (fibronectin 1) is higher than in those who died from other causes. The FN1 gene is known to be a candidate gene for IHD [48].…”

Section: Dna Methylation and Ischemic Heart Diseasementioning

confidence: 99%

“…Troponin subunit [33] PLA2G7 -phospholipase A2 group VII; 6p12.3 Degradation of platelet activating factor [35] MMP9 -matrix metallopeptidase 9; 20q13.12 Degradation of collagen of IV and V types Hypomethylation of the gene promoter is associated with IHD, higher levels of PTX3 protein in the blood plasma [28] The level of PTX3 protein in the blood plasma is higher in the group with fatal ACS related to coronary thrombosis as compared with the control group [29] as well as in persons with advanced endpoints (including cardiac death) related to the chronic heart failure [30] MMP9 -matrix metallopeptidase 9; 20q13.12 Gene methylation is associated with the risk of IHD, age when it started developing, IHD risk factors [24] The level of MMP-9 in the blood plasma is considered as a risk marker for SCD [39] FN1 -fibronectin 1; 2q35 Gene promoter hypermethylation is associated with IHD [47] Gene expression is higher in people with SCD, type 2 diabetes mellitus, and preserved left ventricular ejection fraction as compared with persons who died from another cause [48] F2RL3 -F2R like thrombin or trypsin receptor 3; 19p13.11 Gene methylation is associated with cardiovascular mortality in case of IHD [50] ABCB1 -ATP binding cassette subfamily B member 1; 7q21.12 Gene promoter methylation is associated with the risk of ischemic events (including cardiac death, myocardial infarction, ischemic stroke) in case of intracranial stenosis [52] FOXP3 -forkhead box P3; Xp11.23 Gene hypermethylation is associated with IHD [17]…”

Section: Gck -Glucokinase; 7p13mentioning

confidence: 99%

Role of DNA Methylation in Development of Cardiovascular Diseases, Resulting in a Sudden Cardiac Death (Review)

Иванова¹,

Maksimova²,

Gurazheva³

2022

Sovrem Tehnol Med

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An effective system to diagnose predisposition to development of sudden cardiac death (SCD) is required in order to determine the risk of developing a sudden fatal outcome well in advance of the onset thereof, including in people with asymptomatic cardiovascular disease, as well as to implement early preventive measures that can result in a decrease in the population mortality from cardiovascular diseases. Thus, the search for SCD risk markers becomes a topical issue for modern health care.According to recent studies, epigenetic mechanisms of heredity, and DNA methylation above all, play an important role in development of many diseases. The review provides the results of recent foreign and Russian studies on identification of a link between DNA methylation and development of cardiovascular diseases being the basis for SCD (IHD, cardiomyopathies, heart rhythm disturbances). The major part of the review is dedicated to studying DNA methylation in IHD, which is the most epigenetically explored nosology at the moment. Attention is also paid to studies of the DNA methylation role in development of acute coronary syndrome and myocardial infarction, which have development mechanisms similar to those of SCD. There were only few studies on identification of a link between DNA methylation and cardiomyopathies and cardiac arrhythmias conducted, however, an association of specific genes methylation with the explored nosologies was revealed. The review also provides pathogenetic substantiations of the possibilities to use epigenetic markers of cardiovascular diseases as SCD markers.Thus, it has been established that study of genes the methylation of which is associated with IHD (CTH, PLCB1, PTX3, MMP9, FN1, F2RL3, ABCB1, FOXP3, GDF15, IL6, CASR), with lipid metabolism disorders and atherosclerosis (CETP, CCL2, SREBF2, TIMP1), as well as with heart rhythm disturbances (SCN5A and KCNQ1), may be most promising in relation to SCD.

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“…Low density lipoprotein (LDL) receptor (Ldlr) plays a key role in the regulation of cholesterol metabolism by removing excess low density lipoprotein cholesterol from the circulation [72]. However, in pathological conditions, a high expression level of Ldlr is a risk factor [73,74]. Oxidized LDL and its receptor Olr1 may play a role in a proinflammatory phenotype in pulmonary arterial hypertension [75].…”

Section: Comparison Of Degs Between Moderate and High-intensity Exercisementioning

confidence: 99%

Time-dependent Effects of Moderate- and High-intensity Exercises on Myocardial Transcriptomics

Pang

et al. 2022

Int J Sports Med

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The heart is a highly adaptable organ that responds to changes in functional requirements due to exposure to internal and external stimuli. Physical exercise has unique stimulatory effects on the myocardium in both healthy individuals and those with health disorders, where the effects are primarily determined by the intensity and recovery time of exercise. We investigated the time-dependent effects of different exercise intensities on myocardial transcriptional expression in rats. Moderate intensity exercise induced more differentially expressed genes in the myocardium than high intensity exercise, while 16 differentially expressed genes were down-regulated by moderate intensity exercise but up-regulated by high intensity exercise at 12 h post- exercise. Both Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicated that moderate intensity exercise specifically regulated gene expression related to heart adaptation, energy metabolism, and oxidative stress, while high intensity exercise specifically regulated gene expression related to immunity, inflammation, and apoptosis. Moreover, there was increased expression of Tbx5, Casq1, Igsf1, and Ddah1 at all time points after moderate intensity exercise, while there was increased expression of Card9 at all time points after high intensity exercise. Our study provides a better understanding of the intensity dependent effects of physical exercise of the molecular mechanisms of cardiac adaptation to physical exercise.

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Osteopontin and LDLR Are Upregulated in Hearts of Sudden Cardiac Death Victims With Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus

Cited by 7 publications

References 32 publications

Identification and external validation of the hub genes associated with cardiorenal syndrome through time-series and network analyses

Identification and external validation of the hub genes associated with cardiorenal syndrome through time-series and network analyses

Role of DNA Methylation in Development of Cardiovascular Diseases, Resulting in a Sudden Cardiac Death (Review)

Time-dependent Effects of Moderate- and High-intensity Exercises on Myocardial Transcriptomics

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