Estrogenic hormone action in the heart: regulatory network and function

doi:10.1016/S0008-6363(01)00526-0

Cardiovascular Research 2002 53(3):709-719; doi:10.1016/S0008-6363(01)00526-0
© 2002 by European Society of Cardiology

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Estrogenic hormone action in the heart: regulatory network and function

Fawzi A Babiker^a, Leon J De Windt^a, Martin van Eickels^b, Christian Grohe^c, Rainer Meyer^c and Pieter A Doevendans^a^,d^,*

^aDepartment of Cardiology, Cardiovascular Research Institute Maastricht, University Hospital Maastricht, P. Debyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands
^bTufts University School of Medicine, Boston, MA, USA
^cInstitute of Physiology, Medical Clinic University Bonn, Bonn, Germany
^dInter-universitary Cardiology Institute, Maastricht, The Netherlands

^* Corresponding author. Tel.: +31-43-387-5095; fax: +31-43-387-104 p.doevendans{at}cardio.azm.nl

Cardiovascular diseases are the leading cause of death in theindustrialised countries and display significant gender-baseddifferences. Estrogen plays an important role in the pathogenesisof heart disease and is able to modulate the progression ofcardiovascular disease. The focus on the beneficial influenceof estrogen is gradually shifting from the vascular system tothe myocardium. The presence of functional estrogen receptorsin the myocardium has been demonstrated. Estrogen is importantfor cardiovascular baseline physiology and modulates the myocardialresponse under pathological conditions. Here we summarise thecurrent knowledge of the regulatory network of estrogenic actionin the myocardium and its effects on cardiovascular function.

KEYWORDS ACE, angiotensin converting enzyme; AF-1, trans-activation function-1; AF-2, trans-activation function-2; ANF, atrial natriuretic factor; Ang, angiotensin; CAD, coronary artery disease; CHD, coronary heat disease; cGK, cyclic GMP-dependent protein kinase; cGMP, cyclic guanosine monophosphate; DBD, DNA binding domain; estrogen, 17β-estradiol; EGF, epidermal growth factor; eNOS, endothelial nitric oxide synthase; Egr, early growth response factor; ERT, estrogen replacement therapy; ER, estrogen receptors; ERE, estrogen response element; ERK, extracellular related kinase; ERKO, estrogen receptor knockout mouse; ERRs, estrogen receptor-related receptors; GH, growth hormone; HBD, hormone binding domain; HDL, high density lipoprotein cholesterol; HRT, hormone replacement therapy; HSP, heat shock proteins; IGF-1, insulin-like growth factor; IGF-1R, insulin-like growth factor receptor; Int, initiator of transcription; iNOS, inducible nitric oxide synthase; JNK, C-jun N-terminal kinase; LDL, low density lipoprotein cholesterol; LVH, left ventricular hypertrophy; MAPK, mitogen activated protein kinase; MHC, myosin heavy chain; MI, myocardial infarction; MLC2a, myosin light chain-2a; NO, nitric oxide; NOS, nitric oxide synthase; NR, nuclear receptor; SHR, spontaneous hypertensive rat; SERM, selective estrogen receptor modulator; TAC, transverse aortic construction

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