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Review
. 2022 Jun 1;9(6):174.
doi: 10.3390/jcdd9060174.

A Comprehensive Outlook on Dilated Cardiomyopathy (DCM): State-Of-The-Art Developments with Special Emphasis on OMICS-Based Approaches

Vivek Sarohi  1   2 , Shriya Srivastava  1 , Trayambak Basak  1   2
Affiliations
Review

A Comprehensive Outlook on Dilated Cardiomyopathy (DCM): State-Of-The-Art Developments with Special Emphasis on OMICS-Based Approaches

Vivek Sarohi et al. J Cardiovasc Dev Dis. .

Abstract

Dilated cardiomyopathy (DCM) remains an enigmatic cardiovascular disease (CVD) condition characterized by contractile dysfunction of the myocardium due to dilation of the ventricles. DCM is one of the major forms of CVD contributing to heart failure. Dilation of the left or both ventricles with systolic dysfunction, not explained by known causes, is a hallmark of DCM. Progression of DCM leads to heart failure. Genetic and various other factors greatly contribute to the development of DCM, but the etiology has still remained elusive in a large number of cases. A significant number of studies have been carried out to identify the genetic causes of DCM. These candidate-gene studies revealed that mutations in the genes of the fibrous, cytoskeletal, and sarcomeric proteins of cardiomyocytes result in the development of DCM. However, a significant proportion of DCM patients are idiopathic in nature. In this review, we holistically described the symptoms, causes (in adults and newborns), genetic basis, and mechanistic progression of DCM. Further, we also summarized the state-of-the-art diagnosis, available biomarkers, treatments, and ongoing clinical trials of potential drug regimens. DCM-mediated heart failure is on the rise worldwide including in India. The discovery of biomarkers with a better prognostic value is the need of the hour for better management of DCM-mediated heart failure patients. With the advent of next-generation omics-based technologies, it is now possible to probe systems-level alterations in DCM patients pertaining to the identification of novel proteomic and lipidomic biomarkers. Here, we also highlight the onset of a systems-level study in Indian DCM patients by applying state-of-the-art mass-spectrometry-based "clinical proteomics" and "clinical lipidomics".

Keywords: biomarkers; dilated cardiomyopathy (DCM); gene; heart failure; lipidomics; mechanism; proteomics; treatment.

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Conflict of interest statement

Authors declare no conflict of interest.

Figures

Figure 1
Figure 1
This map of India (modified from Global Burden of Disease; GBD) shows the increase in the incidence of DCM in India in years between 1990 to 2019. There were 106,460 new cases in 1990. Incidents massively increased and 150,507 new cases were reported in 2005. Spike in incidence increased further and 207,168 new cases were reported in 2019. This data clearly indicates that the incidence of DCM is increasing at an alarming rate in India [Adapted with permission from IHME, Seattle, DC, USA “Source: Institute for Health Metrics Evaluation. Used with permission. All rights reserved” [15]. Accessed on 18 April 2021.
Figure 2
Figure 2
Location of proteins in cardiomyocytes that are responsible for development of dilated cardiomyopathy. The figure depicts the spatial location of the cytosolic and sarcomeric proteins encoded by corresponding genes. Mutations in these genes contribute to development of dilated cardiomyopathy. The T-tubule has a large number of ion channels and transporters. T-tubule regulates the calcium concentration in cardiomyocytes and transmits the action potential into the cardiomyocyte. RyR (ryanodine receptor) in sarcoplasmic reticulum (SR) of cardiomyocyte interacts with T-tubule for action potential transmission and RyR is responsible for release of stored calcium from SR. Calcium and ATPs are utilized by sarcomere in contraction. After contraction, calcium released from sarcomere is stored in SR through SERCA. Sarcolemmal and cytoskeletal proteins maintain architecture and functions of cardiomyocytes. Mutation in any of these protein-encoding genes leads to dilated cardiomyopathy.
Figure 3
Figure 3
In DCM, cardiomyocytes undergo apoptosis and proliferation of cardiac fibroblasts to myofibroblasts causes fibrosis in the left ventricle of the heart. These processes lead to left ventricle dilation and wall thinning.
Figure 4
Figure 4
Cardiomyocytes can undergo apoptosis through extrinsic or intrinsic apoptosis pathways. Death receptors mediate the extrinsic apoptosis pathway and various factors including mechanical stress, oxidative stress, DNA damage, growth factors and hormones induce the intrinsic cardiomyocyte apoptosis pathway.
Figure 5
Figure 5
TGF-β can induce cardiac fibroblast proliferation through SMAD-dependent and SMAD-independent pathways, while proliferation through Ang-II is mediated by PLC, DAG, IP3 and PKC.
See this image and copyright information in PMC

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