Document Detail


Role of estrogen in diastolic dysfunction.
MedLine Citation:
PMID:  24414072     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The prevalence of left ventricular diastolic dysfunction (LVDD) sharply increases in women after menopause and may lead to heart failure. While evidence suggests that estrogens protect the premenopausal heart from hypertension and ventricular remodeling, the specific mechanisms involved remain elusive. Moreover, whether there is a protective role of estrogens against cardiovascular disease, and specifically LVDD, continues to be controversial. Clinical and basic science have implicated activation of the renin-angiotensin-aldosterone system (RAAS), linked to the loss of ovarian estrogens, in the pathogenesis of postmenopausal diastolic dysfunction. As a consequence of increased tissue ANG II and low estrogen, a maladaptive nitric oxide synthase (NOS) system produces ROS that contribute to female sex-specific hypertensive heart disease. Recent insights from rodent models that mimic the cardiac phenotype of an estrogen-insufficient or -deficient woman (e.g., premature ovarian failure or postmenopausal), including the ovariectomized congenic mRen2.Lewis female rat, provide evidence showing that estrogen modulates the tissue RAAS and NOS system and related intracellular signaling pathways, in part via the membrane G protein-coupled receptor 30 (GPR30; also called G protein-coupled estrogen receptor 1). Complementing the cardiovascular research in this field, the echocardiographic correlates of LVDD as well as inherent limitations to its use in preclinical rodent studies will be briefly presented. Understanding the roles of estrogen and GPR30, their interactions with the local RAAS and NOS system, and the relationship of each of these to LVDD is necessary to identify new therapeutic targets and alternative treatments for diastolic heart failure that achieve the cardiovascular benefits of estrogen replacement without its side effects and contraindications.
Authors:
Zhuo Zhao; Hao Wang; Jewell A Jessup; Sarah H Lindsey; Mark C Chappell; Leanne Groban
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2014-01-10
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  306     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2014 Mar 
Date Detail:
Created Date:  2014-03-03     Completed Date:  2014-04-24     Revised Date:  2014-06-09    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H628-40     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Age Factors
Animals
Diastole* / drug effects
Disease Models, Animal
Estrogen Replacement Therapy
Estrogens / deficiency,  metabolism*,  therapeutic use
Female
Humans
Myocardium / metabolism*
Nitric Oxide Synthase / metabolism
Postmenopause / metabolism
Reactive Oxygen Species / metabolism
Receptors, Estrogen / metabolism
Receptors, G-Protein-Coupled / metabolism
Renin-Angiotensin System
Risk Factors
Sex Factors
Signal Transduction
Ventricular Dysfunction, Left / drug therapy,  etiology,  metabolism*,  physiopathology,  ultrasonography
Ventricular Function, Left* / drug effects
Grant Support
ID/Acronym/Agency:
AG-033727/AG/NIA NIH HHS; AG-042758/AG/NIA NIH HHS; HL-103974/HL/NHLBI NIH HHS; HL-56793/HL/NHLBI NIH HHS; P30 GM103337/GM/NIGMS NIH HHS; R00 HL103974/HL/NHLBI NIH HHS; R01 AG033727/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Estrogens; 0/GPER protein, human; 0/Reactive Oxygen Species; 0/Receptors, Estrogen; 0/Receptors, G-Protein-Coupled; EC 1.14.13.39/Nitric Oxide Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Inhibition of NADPH oxidase prevents acute lung injury in obese rats following severe trauma.
Next Document:  Why are sex and gender important to basic physiology and translational and individualized medicine?