RNA-seq profiling reveals different pathways between remodeled vessels and myocardium in hypertrophic cardiomyopathy

IF 1.9 4区医学 Q3 HEMATOLOGY Microcirculation Pub Date : 2022-10-05 DOI:10.1111/micc.12790

Annalinda Pisano, Loredana Le Pera, Raffaella Carletti, Bruna Cerbelli, Maria G. Pignataro, Angelina Pernazza, Fabrizio Ferre, Maria Lombardi, Davide Lazzeroni, Iacopo Olivotto, Ornella E. Rimoldi, Chiara Foglieni, Paolo G. Camici, Giulia d'Amati

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引用次数: 1

Abstract

Objective

Coronary microvascular dysfunction (CMD) is a key pathophysiological feature of hypertrophic cardiomyopathy (HCM), contributing to myocardial ischemia and representing a critical determinant of patients' adverse outcome. The molecular mechanisms underlying the morphological and functional changes of CMD are still unknown. Aim of this study was to obtain insights on the molecular pathways associated with microvessel remodeling in HCM.

Methods

Interventricular septum myectomies from patients with obstructive HCM (n = 20) and donors' hearts (CTRL, discarded for technical reasons, n = 7) were collected. Remodeled intramyocardial arterioles and cardiomyocytes were microdissected by laser capture and next-generation sequencing was used to delineate the transcriptome profile.

Results

We identified 720 exclusive differentially expressed genes (DEGs) in cardiomyocytes and 1315 exclusive DEGs in remodeled arterioles of HCM. Performing gene ontology and pathway enrichment analyses, we identified selectively altered pathways between remodeled arterioles and cardiomyocytes in HCM patients and controls.

Conclusions

We demonstrate the existence of distinctive pathways between remodeled arterioles and cardiomyocytes in HCM patients and controls at the transcriptome level.

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RNA-seq分析揭示了肥厚性心肌病重构血管和心肌之间的不同途径

目的冠状动脉微血管功能障碍(CMD)是肥厚性心肌病(HCM)的关键病理生理特征，有助于心肌缺血，是患者不良结局的关键决定因素。其形态和功能变化的分子机制尚不清楚。本研究的目的是了解HCM微血管重构的相关分子途径。方法收集梗阻性HCM患者(n = 20)的室间隔肌瘤切除术和供体心脏(CTRL，因技术原因丢弃，n = 7)。重构的心内小动脉和心肌细胞通过激光捕获进行显微解剖，并使用下一代测序来描绘转录组谱。结果在心肌细胞中鉴定出720个特异性差异表达基因(deg)，在HCM重构小动脉中鉴定出1315个特异性差异表达基因(deg)。通过基因本体论和途径富集分析，我们在HCM患者和对照组中发现了重构小动脉和心肌细胞之间选择性改变的途径。在转录组水平上，我们证明了HCM患者和对照组中重构小动脉和心肌细胞之间存在不同的通路。

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来源期刊

Microcirculation 医学-外周血管病

CiteScore

5.00

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation. Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.