Molecular mechanisms of remodeling in human atrial fibrillation

BJJM Brundel*, RH Henning, HH Kampinga, IC Van Gelder, HJGM Crijns

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

99 Citations (Scopus)

Abstract

An important acknowledgement of the last several years is that atrial fibrillation (AF) modifies the electrical properties of the atrium in a way that promotes its occurrence and maintenance. This arrhythmogenic electrophysiological remodeling is well established, but can not explain by itself that 'AF begets AF'. This review describes molecular changes involving rapid functional alterations and slower changes in protein expression that cause electrical remodeling and contractile dysfunction in AF. An important molecular feature of AF is the reduction in L-type Ca(2+) channel function and protein expression. This reduction may serve to protect the cell against a potentially lethal Ca(2+) overload resulting from the increased activation rate in AF. Further, the review discusses the possible role of proteolytic systems. notably the calpains. as a mechanism linking Ca(2+) overload to reduced protein expression. Thus. it appears that the elaborate molecular changes in AF are directed primarily at protecting the myocyte from cellular stress, However, such early protection occurs at the expense of electrophysiological changes that promote the long-term maintenance of AF. (C) 2002 Elsevier Science B.V. All rights reserved.

Original languageEnglish
Article numberPII S0008-6363(02)00222-5
Pages (from-to)315-324
Number of pages10
JournalCardiovascular Research
Volume54
Issue number2
Publication statusPublished - May-2002

Keywords

  • ion channels
  • contractile function
  • arrhythmia (mechanisms)
  • ACTIVATED NEUTRAL PROTEASE
  • CHRONIC DOG-MODEL
  • CONTRACTILE DYSFUNCTION
  • ELECTRICAL CARDIOVERSION
  • GENE-EXPRESSION
  • MESSENGER-RNA
  • CELL-DEATH
  • ELECTROPHYSIOLOGICAL CHARACTERISTICS
  • STRUCTURAL-CHANGES
  • REFRACTORY PERIOD

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