Shared Molecular Mechanisms of Hypertrophic Cardiomyopathy and Its Clinical Presentations: Automated Molecular Mechanisms Extraction Approach.

Mila Glavaški,Lazar Velicki

doi:10.3390/life11080785

Mila Glavaški, Lazar Velicki

Open Access

https://doi.org/10.3390/life11080785

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Abstract

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease with a prevalence of 1 in 500 people and varying clinical presentations. Although there is much research on HCM, underlying molecular mechanisms are poorly understood, and research on the molecular mechanisms of its specific clinical presentations is scarce. Our aim was to explore the molecular mechanisms shared by HCM and its clinical presentations through the automated extraction of molecular mechanisms. Molecular mechanisms were congregated by a query of the INDRA database, which aggregates knowledge from pathway databases and combines it with molecular mechanisms extracted from abstracts and open-access full articles by multiple machine-reading systems. The molecular mechanisms were extracted from 230,072 articles on HCM and 19 HCM clinical presentations, and their intersections were found. Shared molecular mechanisms of HCM and its clinical presentations were represented as networks; the most important elements in the intersections’ networks were found, centrality scores for each element of each network calculated, networks with reduced level of noise generated, and cooperatively working elements detected in each intersection network. The identified shared molecular mechanisms represent possible mechanisms underlying different HCM clinical presentations. Applied methodology produced results consistent with the information in the scientific literature.

Highlights

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease [1,2,3], with an estimated prevalence of 1 in 500 people worldwide [1,3,4,5] and recent investigations suggesting an even greater prevalence [5,6]
Molecular mechanisms from all PubMed articles published starting from 1 January 2010 were separately extracted in the form of INDRA statements [30] for HCM, cardiomyocyte hypertrophy, myofibrillar disarray, cardiomyocyte disarray, myocardial remodeling, cardiac remodeling, myocardial fibrosis, left ventricular outflow tract obstruction (LVOTO), myocardial hypercontractility, impaired myocardial relaxation, impaired cardiac relaxation, myocardial stiffness, diastolic dysfunction, atrial fibrillation (AF), sudden cardiac death (SCD), coronary microvascular dysfunction, myocardial ischemia, heart failure (HF), Major adverse cardiovascular events (MACE), and rehospitalization
PubMed Identifiers (PMIDs) were collected through the INDRA PubMed client [30] using the following search terms: hypertrophic cardiomyopathy, cardiomyocyte hypertrophy, myofibrillar disarray, cardiomyocyte disarray, myocardial remodeling, cardiac remodeling, myocardial fibrosis, left ventricular outflow tract obstruction, myocardial hypercontractility, impaired myocardial relaxation, impaired cardiac relaxation, myocardial stiffness, diastolic dysfunction, atrial fibrillation, sudden cardiac death, coronary microvascular dysfunction, myocardial ischemia, heart failure, major adverse cardiovascular events, and rehospitalization

Summary

Introduction

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease [1,2,3], with an estimated prevalence of 1 in 500 people worldwide [1,3,4,5] and recent investigations suggesting an even greater prevalence [5,6]. It is characterized by increased left ventricular wall thickness that cannot be explained by abnormal loading conditions (e.g., hypertension) [1,2,7].

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