Microvascular Rarefaction and Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy

Tian, Hongwei; Yang, Chengzhi; Song, Yang; Wang, Hongyue; Yuan, Jiansong; Cui, Jingang; Liu, Shengwen; Hu, Fenghuan; Yang, Wei; Jiang, Xiaowei; Qiao, Shubin

doi:10.1159/000493005

Cited by 7 publications

(9 citation statements)

References 34 publications

(34 reference statements)

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“…In this study, we found that the microvessel density in myocardium of cTNTQ92 transgenic mice was signi cantly lower. This observations is consistent with our previous ndings for human HCM myocardium [4]. We also found the expression levels of both CD36 mRNA and CD36 protein in the myocardium of cTNTQ92 transgenic mice were signi cantly higher than those of the control group, which suggest that CD36 expression levels may be associated with angiogenesis in HCM.…”

Section: Discussionsupporting

confidence: 93%

Down-regulation CD36 increased proliferation of endothelial cell in hypertrophic cardiomyopathy

Tian

Yang

Wang

et al. 2023

Preprint

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Background: Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease caused by genetic mutations. HCM with normal epicardial coronary arteries often reveal microvascular rarefaction and myocardial ischemia.Cluster of differentiation 36 (CD36) is a multifunctional pattern recognition membrane receptor that is highly expressed on microvascular endothelial cells (MVEC) and plays an essential role in endothelial cell function. However,whether CD36 affects vascular endothelial cell proliferation in HCM is unclear.We detected the effects of CD36 on endothelial cell proliferation and it’s underlying mechanisms in HCM. Methods: We detected the effects of CD36 on endothelial cell proliferation and it’s underlying mechanisms in HCM. These studies were complemented by in vivo analysis of CD36 expression in cTnTQ92 transgenic mice myocardium and in vitro analysis of transfection of CD36 gene or SiRNA-CD36 to endothelial cells isolated from cTnTQ92 transgenic mice heart. Results: In this study, we found that the expression of CD36 was higher and the microvessel density was lower in myocardial tissue of cTnTQ92 transgenic mice than that in the myocardial tissue of wild-type control C57BL/6 mice. The expressions of CD36 and p21 in endothelial cells isolated from cTnTQ92 transgenic mice heart were higher than those in control group. The expression levels of proliferating cell nuclear antigen (PCNA) and Cyclin D1 proteins were lower than that of control group, and the proliferation of endothelial cells was lower than that of control group, but the opposite results were obtained by transfection of SiRNA-CD36 to endothelial cells. Further studies showed that down-regulation of CD36 increased the expression of p-VEGFR2 and increased proliferation of endothelial cell. EGFR specific inhibitor AG1478 reversed these effects. Conclusions: These findings suggest down-regulation of CD36 increased the expression of p-VEGFR2 and increased proliferation of endothelial cell in hypertrophic cardiomyopathy. Down-regulation CD36 expression may be a potential therapeutic strategy for the treatment of myocardial ischemia in HCM.

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Section: Discussionsupporting

confidence: 93%

Down-regulation CD36 increased proliferation of endothelial cell in hypertrophic cardiomyopathy

Tian

Yang

Wang

et al. 2023

Preprint

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“…Dysfunction of coronary microvasculature is also a major change in heart during HCM and myocardial fibrosis (24,25). PDGFR is widely studied in multiple pathological processes such as cancer, fibrosis, and atherosclerosis and functions through promoting cell proliferation, angiogenesis, and many other cell behaviors; therefore, it is regarded as an ideal candidate for drug development (26,27).…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential miRNA-mRNA Regulatory Network Contributing to Hypertrophic Cardiomyopathy (HCM)

Wang

2021

Front. Cardiovasc. Med.

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Background: Hypertrophic cardiomyopathy (HCM) is a myocardial disease with unidentified pathogenesis. Increasing evidence indicated the potential role of microRNA (miRNA)-mRNA regulatory network in disease development. This study aimed to explore the miRNA-mRNA axis in HCM.Methods: The miRNA and mRNA expression profiles obtained from the Gene Expression Omnibus (GEO) database were used to identify differentially expressed miRNAs (DEMs) and genes (DEGs) between HCM and normal samples. Target genes of DEMs were determined by miRTarBase. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to identify biological functions of the DEGs and DEMs. miRNA-mRNA regulatory network was constructed to identify the hub genes and miRNAs. Logistic regression model for HCM prediction was established basing on the network.Results: A total of 224 upregulated and 366 downregulated DEGs and 10 upregulated and 14 downregulated DEMs were determined. We identified 384 DEM-targeted genes, and 20 of them were overlapped with the DEGs. The enriched functions include extracellular structure organization, organ growth, and phagosome and melanoma pathways. The four miRNAs and three mRNAs, including hsa-miR-373, hsa-miR-371-3p, hsa-miR-34b, hsa-miR-452, ARHGDIA, SEC61A1, and MYC, were identified through miRNA-mRNA regulatory network to construct the logistic regression model. The area under curve (AUC) values over 0.9 suggested the good performance of the model.Conclusion: The potential miRNA-mRNA regulatory network and established logistic regression model in our study may provide promising diagnostic methods for HCM.

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“…Microvasculature included capillaries (area 10-78.5 μm 2 , lumen diameter <10 μm) and precapillary arteries (area 78.5-314 μm 2 , lumen diameter <10-20 μm), microvessels were tagged by the pathologists on the monitor image and counted in 6 fields at ×200 magnification using Image-Pro Plus 6.0 image analysis software (Media Cybernetics Inc., Buckinghamshire, UK) to calculate microvessels. Finally, the mean number of microvessels per square millimeter was calculated and expressed as the MVD [Tian 2018].…”

Section: Surgical Techniquementioning

confidence: 99%

“…The slice was put in acid water and phosphomolybdic acid (1 min), and then aniline blue was added and washed with acid water. Six fields of view randomly were selected at ×200 magnification, and the percentage (%) of the area of fibrosis was calculated after labeling by a pathologist using Image-Pro Plus 6.0 image analysis software (Media Cybernetics Inc., Buckinghamshire, UK) [Tian 2018].…”

Section: Surgical Techniquementioning

confidence: 99%

“…Myocardial capillary density is about 3000-4000/mm 3 under normal conditions, and blood flow increases sixfold in emergencies situations to accommodate energy demands [Marszalek 2019]. A study of postoperative myocardial tissue in patients with hypertrophic cardiomyopathy revealed a significant decrease in cardiac capillary density, accompanied by an increase in the area of myocardial fibrosis [Tian 2018]. But it is unclear, however, whether and to what extent pathological diffuse fibrosis occurs in childhood HCOM.…”

Section: Introductionmentioning

confidence: 99%

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Microvascular Rarefaction and Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy: A Histopathological Comparison of Pediatric and Adult Patients

Zhang

Han

et al. 2022

HSF

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Background: Hypertrophic obstructive cardiomyopathy (HOCM) is a genetic cardiomyopathy characterized by microvascular ischemia and myocardial fibrosis. Microvessels play an important role in myocardial fibrosis in HOCM. However, the changes of myocardial microvessels and myocardial fibrosis in pediatric and adult patients with HOCM remain unclear. This study was to investigate the changes in myocardial microvessel density (MVD) and myocardial fibrosis in pediatric and adult patients with HOCM. Methods: We analyzed the changes in MVD and myocardial fibrosis in myectomy left ventricular (LV) septal wall specimens in 12 adult patients and five pediatric patients with HOCM. Control myocardium from the LV septal wall was collected at autopsy of 5 adults and 4 pediatric individuals, who died of non-cardiac causes. Results: There was no significant difference in MVD between pediatric HOCM patients and control subjects (706.4±187.5 vs. 940.2±491.1, P > 0.05), but the myocardial fibrosis area ratio was significantly increased in HOCM than in control subjects (10.6±3.5 vs. 4.9±1.2, P < 0.01). MVD was significantly reduced, and myocardial fibrosis area ratio was significantly higher in adult HOCM patients than in control subjects (i.e. 523.3± 209.4 vs. 845.7±260.7, P < 0.05; 12.8±5.1 vs. 4.4±1.3, P < 0.05). There was no significant difference in MVD and myocardial fibrosis between pediatric and adult HOCM patients (706.4±187.5 vs. 523.3±209.4, P > 0.05; 10.6±3.5 vs. 12.8±5.1, P > 0.05). Conclusions: Pediatric and adult patients with HOCM have high myocardial fibrosis. The present findings suggest that myocardial microvascular density lesions contribute to myocardial fibrosis during childhood.

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Microvascular Rarefaction and Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy

Cited by 7 publications

References 34 publications

Down-regulation CD36 increased proliferation of endothelial cell in hypertrophic cardiomyopathy

Down-regulation CD36 increased proliferation of endothelial cell in hypertrophic cardiomyopathy

Identification of Potential miRNA-mRNA Regulatory Network Contributing to Hypertrophic Cardiomyopathy (HCM)

Microvascular Rarefaction and Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy: A Histopathological Comparison of Pediatric and Adult Patients

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