Ischemic heart disease induces upregulation of endothelin receptor mRNA in human coronary arteries.
Endothelin has been implicated in the pathogenesis of ischemic heart disease and congestive heart failure. The aims were to quantify endothelin type A (ETA) and type B (ETB) receptor mRNA levels in human coronary arteries from patients with ischemic heart disease, congestive heart failure and controls using real-time polymerase chain reaction (real-time PCR). In addition, the suitability of organ culture as a model mimicking endothelin receptor changes in cardiovascular disease was evaluated by in vitro pharmacology and real-time PCR. Endothelin ETA and ETB receptor mRNA levels were significantly higher in arteries from patients with ischemic heart disease (0.23+/-0.04 and 0.35+/-0.06) as compared to congestive heart failure (0.09+/-0.02 and 0.07+/-0.01) and controls (0.08+/-0.02 and 0.08+/-0.01). After organ culture, the endothelin ETB receptor mRNA levels were elevated, and the sarafotoxin 6c-induced vasoconstriction was more efficacious. Increased endothelin receptor activity may contribute to the increased vascular tone and development of atherosclerotic disease in ischemic heart disease in man.
Wackenfors
Angelica
A
Department of Internal Medicine, Division of Experimental Vascular Research, BMC A13, Lund University Hospital, SE-221 84, Lund, Sweden. angelica.wackenfors@med.lu.se
Emilson
Malin
M
Ingemansson
Richard
R
Hortobagyi
Tibor
T
Szok
Delia
D
Tajti
Janos
J
Vecsei
Laszlo
L
Edvinsson
Lars
L
Malmsjö
Malin
M
D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000819:agonists / Q000096:biosynthesis*; D044022:Receptor, Endothelin A / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics; D044023:Receptor, Endothelin B / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B