Genetically changed mice with chronic deficiency or overexpression of the beta-adrenoceptors--what can we learn for the therapy of heart failure?
Heart failure is one of the most common medical diseases-almost every third 55-year-old person in the Western world is going to develop heart failure in his or her life. The development of heart failure is associated with pivotal restructuring of the beta-adrenergic system. The beta-adrenoceptor antagonists have emerged to be an essential part of the therapy of chronic heart failure. Three different beta-adrenoceptors could be identified and characterized so far. The beta1-adrenoceptors are being down-regulated, while the beta3-adrenoceptors are being up-regulated. The mechanisms that are responsible for the positive impact of beta-adrenoceptor antagonists are not completely understood up to now. Therefore, it is necessary to point out the crucial role of the beta-adrenergic system for the regulation of the cardiovascular system and the pathogenesis of heart failure. In the recent couple of years, numerous transgenic mouse models have proven to be helpful to gain a better understanding of the function and the relevance of these receptors. This review gives an overview of the pathophysiological relevance of the beta-adrenergic system for heart failure and outlines the most important insights concerning heart function, which could be derived from genetically changed mice with chronic deficiency and overexpression of the beta-adrenoceptor.
Lee
Samuel
S
Laboratory of Muscle Research and Molecular Cardiology, Department III for Internal Medicine, University of Cologne, Cologne, Germany.
Schwinger
Robert H G
RH
Brixius
Klara
K
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D006333:Heart Failure / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011943:Receptors, Adrenergic, beta / Q000235:genetics*
D011943:Receptors, Adrenergic, beta