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

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

doi:10.1111/micc.12790

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

Microcirculation. 2022 Nov;29(8):e12790. doi: 10.1111/micc.12790. Epub 2022 Oct 14.

Authors

Annalinda Pisano¹, Loredana Le Pera^{2

3}, Raffaella Carletti⁴, Bruna Cerbelli⁵, Maria G Pignataro⁶, Angelina Pernazza⁵, Fabrizio Ferre⁷, Maria Lombardi⁸, Davide Lazzeroni⁸, Iacopo Olivotto⁹, Ornella E Rimoldi¹⁰, Chiara Foglieni⁸, Paolo G Camici^{8

11}, Giulia d'Amati¹

Affiliations

¹ Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy.
² Italian National Institute of Health (ISS), Core Facilities, Rome, Italy.
³ National Research Council (IBIOM-CNR), Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, Bari, Italy.
⁴ Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
⁵ Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
⁶ Department of Chemistry and Drug Technologies, Sapienza University of Rome, Rome, Italy.
⁷ Department of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna, Italy.
⁸ Cardiovascular Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.
⁹ Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy.
¹⁰ National Research Council (IBFM-CNR), Institute of Molecular Bioimaging and Physiology, Milan, Italy.
¹¹ Faculty of Medicine and Surgery, Vita-Salute University, Milan, Italy.

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.

Keywords: coronary microvascular remodeling; hypertrophic cardiomyopathy; pathway enrichment analyses; remodeled arterioles dissected.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cardiomyopathy, Hypertrophic* / genetics
Humans
Microvessels
Myocardial Ischemia*
Myocardium / metabolism
RNA-Seq