Cardiac fibrosis and arrhythmogenesis

My Nhan Nguyen, Helen Kiriazis, Xiao-Ming Gao, Xiao Jun Du

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

Myocardial injury, mechanical stress, neurohormonal activation, inflammation, and/or aging all lead to cardiac remodeling, which is responsible for cardiac dysfunction and arrhythmogenesis. Of the key histological components of cardiac remodeling, fibrosis either in the form of interstitial, patchy, or dense scars, constitutes a key histological substrate of arrhythmias. Here we discuss current research findings focusing on the role of fibrosis, in arrhythmogenesis. Numerous studies have convincingly shown that patchy or interstitial fibrosis interferes with myocardial electrophysiology by slowing down action potential propagation, initiating reentry, promoting after-depolarizations, and increasing ectopic automaticity. Meanwhile, there has been increasing appreciation of direct involvement of myofibroblasts, the activated form of fibroblasts, in arrhythmogenesis. Myofibroblasts undergo phenotypic changes with expression of gap-junctions and ion channels thereby forming direct electrical coupling with cardiomyocytes, which potentially results in profound disturbances of electrophysiology. There is strong evidence that systemic and regional inflammatory processes contribute to fibrogenesis (i.e., structural remodeling) and dysfunction of ion channels and Ca2+ homeostasis (i.e., electrical remodeling). Recognizing the pivotal role of fibrosis in the arrhythmogenesis has promoted clinical research on characterizing fibrosis by means of cardiac imaging or fibrosis biomarkers for clinical stratification of patients at higher risk of lethal arrhythmia, as well as preclinical research on the development of antifibrotic therapies. At the end of this review, we discuss remaining key questions in this area and propose new research approaches.

Original languageEnglish
Pages (from-to)1009-1049
Number of pages41
JournalComprehensive Physiology
Volume7
Issue number3
DOIs
Publication statusPublished - 1 Jul 2017

Cite this

Nguyen, My Nhan ; Kiriazis, Helen ; Gao, Xiao-Ming ; Du, Xiao Jun. / Cardiac fibrosis and arrhythmogenesis. In: Comprehensive Physiology. 2017 ; Vol. 7, No. 3. pp. 1009-1049.
@article{9c469a5e785c4850b2fa03aed588317a,
title = "Cardiac fibrosis and arrhythmogenesis",
abstract = "Myocardial injury, mechanical stress, neurohormonal activation, inflammation, and/or aging all lead to cardiac remodeling, which is responsible for cardiac dysfunction and arrhythmogenesis. Of the key histological components of cardiac remodeling, fibrosis either in the form of interstitial, patchy, or dense scars, constitutes a key histological substrate of arrhythmias. Here we discuss current research findings focusing on the role of fibrosis, in arrhythmogenesis. Numerous studies have convincingly shown that patchy or interstitial fibrosis interferes with myocardial electrophysiology by slowing down action potential propagation, initiating reentry, promoting after-depolarizations, and increasing ectopic automaticity. Meanwhile, there has been increasing appreciation of direct involvement of myofibroblasts, the activated form of fibroblasts, in arrhythmogenesis. Myofibroblasts undergo phenotypic changes with expression of gap-junctions and ion channels thereby forming direct electrical coupling with cardiomyocytes, which potentially results in profound disturbances of electrophysiology. There is strong evidence that systemic and regional inflammatory processes contribute to fibrogenesis (i.e., structural remodeling) and dysfunction of ion channels and Ca2+ homeostasis (i.e., electrical remodeling). Recognizing the pivotal role of fibrosis in the arrhythmogenesis has promoted clinical research on characterizing fibrosis by means of cardiac imaging or fibrosis biomarkers for clinical stratification of patients at higher risk of lethal arrhythmia, as well as preclinical research on the development of antifibrotic therapies. At the end of this review, we discuss remaining key questions in this area and propose new research approaches.",
author = "Nguyen, {My Nhan} and Helen Kiriazis and Xiao-Ming Gao and Du, {Xiao Jun}",
year = "2017",
month = "7",
day = "1",
doi = "10.1002/cphy.c160046",
language = "English",
volume = "7",
pages = "1009--1049",
journal = "Comprehensive Physiology",
issn = "2040-4603",
publisher = "American Physiological Society",
number = "3",

}

Nguyen, MN, Kiriazis, H, Gao, X-M & Du, XJ 2017, 'Cardiac fibrosis and arrhythmogenesis', Comprehensive Physiology, vol. 7, no. 3, pp. 1009-1049. https://doi.org/10.1002/cphy.c160046

Cardiac fibrosis and arrhythmogenesis. / Nguyen, My Nhan; Kiriazis, Helen; Gao, Xiao-Ming; Du, Xiao Jun.

In: Comprehensive Physiology, Vol. 7, No. 3, 01.07.2017, p. 1009-1049.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Cardiac fibrosis and arrhythmogenesis

AU - Nguyen, My Nhan

AU - Kiriazis, Helen

AU - Gao, Xiao-Ming

AU - Du, Xiao Jun

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Myocardial injury, mechanical stress, neurohormonal activation, inflammation, and/or aging all lead to cardiac remodeling, which is responsible for cardiac dysfunction and arrhythmogenesis. Of the key histological components of cardiac remodeling, fibrosis either in the form of interstitial, patchy, or dense scars, constitutes a key histological substrate of arrhythmias. Here we discuss current research findings focusing on the role of fibrosis, in arrhythmogenesis. Numerous studies have convincingly shown that patchy or interstitial fibrosis interferes with myocardial electrophysiology by slowing down action potential propagation, initiating reentry, promoting after-depolarizations, and increasing ectopic automaticity. Meanwhile, there has been increasing appreciation of direct involvement of myofibroblasts, the activated form of fibroblasts, in arrhythmogenesis. Myofibroblasts undergo phenotypic changes with expression of gap-junctions and ion channels thereby forming direct electrical coupling with cardiomyocytes, which potentially results in profound disturbances of electrophysiology. There is strong evidence that systemic and regional inflammatory processes contribute to fibrogenesis (i.e., structural remodeling) and dysfunction of ion channels and Ca2+ homeostasis (i.e., electrical remodeling). Recognizing the pivotal role of fibrosis in the arrhythmogenesis has promoted clinical research on characterizing fibrosis by means of cardiac imaging or fibrosis biomarkers for clinical stratification of patients at higher risk of lethal arrhythmia, as well as preclinical research on the development of antifibrotic therapies. At the end of this review, we discuss remaining key questions in this area and propose new research approaches.

AB - Myocardial injury, mechanical stress, neurohormonal activation, inflammation, and/or aging all lead to cardiac remodeling, which is responsible for cardiac dysfunction and arrhythmogenesis. Of the key histological components of cardiac remodeling, fibrosis either in the form of interstitial, patchy, or dense scars, constitutes a key histological substrate of arrhythmias. Here we discuss current research findings focusing on the role of fibrosis, in arrhythmogenesis. Numerous studies have convincingly shown that patchy or interstitial fibrosis interferes with myocardial electrophysiology by slowing down action potential propagation, initiating reentry, promoting after-depolarizations, and increasing ectopic automaticity. Meanwhile, there has been increasing appreciation of direct involvement of myofibroblasts, the activated form of fibroblasts, in arrhythmogenesis. Myofibroblasts undergo phenotypic changes with expression of gap-junctions and ion channels thereby forming direct electrical coupling with cardiomyocytes, which potentially results in profound disturbances of electrophysiology. There is strong evidence that systemic and regional inflammatory processes contribute to fibrogenesis (i.e., structural remodeling) and dysfunction of ion channels and Ca2+ homeostasis (i.e., electrical remodeling). Recognizing the pivotal role of fibrosis in the arrhythmogenesis has promoted clinical research on characterizing fibrosis by means of cardiac imaging or fibrosis biomarkers for clinical stratification of patients at higher risk of lethal arrhythmia, as well as preclinical research on the development of antifibrotic therapies. At the end of this review, we discuss remaining key questions in this area and propose new research approaches.

UR - http://www.scopus.com/inward/record.url?scp=85021167561&partnerID=8YFLogxK

U2 - 10.1002/cphy.c160046

DO - 10.1002/cphy.c160046

M3 - Article

VL - 7

SP - 1009

EP - 1049

JO - Comprehensive Physiology

JF - Comprehensive Physiology

SN - 2040-4603

IS - 3

ER -