Human genetics and its impact on cardiovascular disease

Tada, Hayato; Fujino, Noboru; Hayashi, Kenshi; Kawashiri, Masa‐aki; Takamura, Masayuki

doi:10.1016/j.jjcc.2021.09.005

Cited by 21 publications

(12 citation statements)

References 72 publications

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“…Briefly, the ventricles were excised and transferred to Hank’s solution (Invitrogen, Thermo Fisher Scientific, Inc., Waltham, MA, USA). Thereafter, cells were isolated and cultured in Dulbecco’s Modified Eagle’s Medium (Gibco, Thermo Fisher Scientific, Inc.) containing 10% fetal bovine serum (Gibco) and 1% penicillinstreptomycin (Gibco) at 37°C with 5% CO 2 in humidified air. Cardiomyocytes were cultured under semiconfluent conditions and transferred to 6-well plates at a density of 2 × 10 5 cells/ml.…”

Section: Methodsmentioning

confidence: 99%

“…Cardiovascular disease has a high incidence worldwide, and some severe cardiovascular diseases are more dangerous than cancer. [1][2][3] Cardiac hypertrophy is an important indicator for judging the pathological process and occurs during ischemic heart disease, hypertension, and heart failure. 4,5 The pathological changes of cardiac hypertrophy include an increase in the size of cardiomyocytes, myocardial interstitial cell proliferation, and cardiac extracellular matrix remodeling.…”

Section: Introductionmentioning

confidence: 99%

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MALAT1 regulates hypertrophy of cardiomyocytes by modulating the miR-181a/HMGB2 pathway

Chen

Zhang

et al. 2022

Eur J Histochem

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Noncoding RNAs are important for regulation of cardiac hypertrophy. The function of MALAT1 (a long noncoding mRNA), miR-181a, and HMGB2; their contribution to cardiac hypertrophy; and the regulatory relationship between them during this process remain unknown. In the present study, we treated primary cardiomyocytes with angiotensin II (Ang II) to mimic cardiac hypertrophy. MALAT1 expression was significantly downregulated in Ang II-treated cardiomyocytes compared with control cardiomyocytes. Ang II-induced cardiac hypertrophy was suppressed by overexpression of MALAT1 and promoted by genetic knockdown of MALAT1. A dual-luciferase reporter assay demonstrated that MALAT1 acted as a sponge for miR-181a and inhibited its expression during cardiac hypertrophy. Cardiac hypertrophy was suppressed by overexpression of a miR-181a inhibitor and enhanced by overexpression of a miR-181a mimic. HMGB2 was downregulated during cardiac hypertrophy and was identified as a target of miR-181a by bioinformatics analysis and a dual-luciferase reporter assay. miR-181a overexpression decreased the mRNA and protein levels of HMGB2. Rescue experiments indicated that MALAT1 overexpression reversed the effect of miR-181a on HMGB2 expression. In summary, the results of the present study show that MALAT1 acts as a sponge for miR-181a and thereby regulates expression of HMGB2 and development of cardiac hypertrophy. The novel MALAT1/miR-181a/HMGB2 axis might play a crucial role in cardiac hypertrophy and serve as a new therapeutic target.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MALAT1 regulates hypertrophy of cardiomyocytes by modulating the miR-181a/HMGB2 pathway

Chen

Zhang

et al. 2022

Eur J Histochem

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“…Various genomics studies have been conducted recently to discover underlying genetic etiology in CVD patients, especially those suspected of HF disease [14]. Several CVDrelated genes have significant mutations and expression differences among CVD patients [15].…”

Section: Introductionmentioning

confidence: 99%

“…Various genomics studies have been conducted recently to discover underlying genetic etiology in CVD patients, especially those suspected of HF disease [14]. Several CVD-related genes have significant mutations and expression differences among CVD patients [15]. In this manuscript, we report a multifaceted approach involving whole-genome sequencing (WGS) integrated with differential gene expression for HF and other CVD study [16, 17].…”

Section: Introductionmentioning

confidence: 99%

Investigating variant and expression of CVD genes associated phenotypes among high-risk Heart Failure patients

Ahmed

Zeeshan

Persaud

et al. 2023

Preprint

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Cardiovascular disease (CVD) is a leading cause of premature mortality in the US and the world. CVD comprises of several complex and mostly heritable conditions, which range from myocardial infarction to congenital heart disease. Here, we report our findings from an integrative analysis of gene expression, disease-causing gene variants, and associated phenotypes among CVD populations, with a focus on high-risk Heart Failure (HF) patients. We built a cohort using electronic health records (EHR) of consented patients with available samples, and then performed high-throughput whole-genome and RNA sequencing (RNA-seq) of key genes responsible for HF and other CVD pathologies. We also incorporated a translational aspect to our study by integrating genomics findings with patient medical records. This involved linking ICD-10 codes with our gene expression and variant data to identify associations with HF and other CVDs. Our in-depth gene expression analysis revealed differentially expressed genes associated with HF (41 genes) and other CVDs (23 genes). Furthermore, a variant analysis of whole-genome sequence data of CVD patients identified genes with altered gene expression (FLNA, CST3, LGALS3, and HBA1) with functional and nonfunctional mutations in these genes. Our study highlights the importance of an integrative approach that leverages gene expression, genetic mutations, and clinical data that will allow the prioritization of key driver genes for complex diseases to improve personalized healthcare.

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“…Availability of large population-based genetic databases has enabled diseases with only a partial genetic basis to be evaluated in terms of future risk and individuals to be risk stratified based on their unique genetic profile. This has given rise to what is termed a ‘polygenic risk score’ (PRS) where a particular combination of genetic variants may confer a specific likelihood of developing a certain polygenic condition, such as hypertension ( Tada et al , 2021 ) or diabetes, later in life ( Konuma and Okada, 2021 ). Furthermore, PRS can be derived for various non-disease-related parameters, including intelligence, height, endurance and even criminality ( Kendler et al , 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Polygenic risk score for embryo selection—not ready for prime time

et al. 2022

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Numerous chronic diseases have a substantial hereditary component. Recent advances in human genetics have allowed the extent of this to be quantified via genome-wide association studies, producing polygenic risk scores (PRS), which can then be applied to individuals to estimate their risk of developing a disease in question. This technology has recently been applied to embryo selection in the setting of IVF and preimplantation genetic testing, with limited data to support its utility. Furthermore, there are concerns that the inherent limitations of PRS makes it ill-suited for use as a screening test in this setting. There are also serious ethical and moral questions associated with this technology that are yet to be addressed. We conclude that further research and ethical reflection are required before embryo selection based on PRS is offered to patients outside of the research setting.

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Human genetics and its impact on cardiovascular disease

Cited by 21 publications

References 72 publications

MALAT1 regulates hypertrophy of cardiomyocytes by modulating the miR-181a/HMGB2 pathway

MALAT1 regulates hypertrophy of cardiomyocytes by modulating the miR-181a/HMGB2 pathway

Investigating variant and expression of CVD genes associated phenotypes among high-risk Heart Failure patients

Polygenic risk score for embryo selection—not ready for prime time

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