Effect of estrogen on calcium-handling proteins, β-adrenergic receptors, and function in rat heart

Chu, Sang Hui; Goldspink, Paul H.; Kowalski, Jill; Beck, Jenny; Schwertz, Dorie W.

doi:10.1016/j.lfs.2006.03.037

Cited by 79 publications

(64 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite the activation of neurohormonal compensatory mechanisms, myocyte contractility is depressed in the infarcted heart, partly due to dysregulation of excitation-contraction (E-C) coupling (8,15,19). The expression of key proteins and the signaling components involved in E-C coupling regulation differ between females and males and are associated with slight functional differences (6). A greater abundance of L-type Ca 2ϩ channel protein and dihydropyridine binding sites in concert with larger Ca 2ϩ current density (I ca ) have been reported in female myocytes (6,35).…”

Section: Discussionmentioning

confidence: 99%

“…The expression of key proteins and the signaling components involved in E-C coupling regulation differ between females and males and are associated with slight functional differences (6). A greater abundance of L-type Ca 2ϩ channel protein and dihydropyridine binding sites in concert with larger Ca 2ϩ current density (I ca ) have been reported in female myocytes (6,35). Expression of several calcium-handling proteins appears to be selectively regulated by estrogen, but the contribution to basal and pathologic contractile function is unclear (7).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Sex-related changes in cardiac function following myocardial infarction in mice

Shioura¹,

Geenen²,

Goldspink³

2008

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Shioura KM, Geenen DL, Goldspink PH. Sex-related changes in cardiac function following myocardial infarction in mice. Am J Physiol Regul Integr Comp Physiol 295: R528 -R534, 2008. First published June 11, 2008 doi:10.1152/ajpregu.90342.2008.-Recent awareness of cardiovascular diseases as a number one killer of the middle-aged women has prompted interest in sex differences leading to heart failure (HF). Therefore, we evaluated cardiac function in female and male mice following myocardial infarction (MI) using the Millar pressure-volume (P-V) conductance system in vivo, at time points corresponding to early (2 wk), late compensatory hypertrophy (4 wk), and decompensation (10 wk) to HF. A significant deterioration of the load dependent and independent hemodynamic measurements occurred in both female and male mice during the early phase of hypertrophy. Later, compensatory hypertrophy was marked by a normalization of volumes to control levels in females compared with males. The most notable differences between sexes occurred in the measurements of cardiac contractility during the decompensation to HF. In females, there was a significant improvement in contractility compared with males, which was apparent in the load-independent measurements of preload recruitable stroke work (10 wk post-MI, female ϭ 48.7 Ϯ 8.0 vs. male ϭ 25.2 Ϯ 1.8 mmHg, P Ͻ 0.05) and maximum dP/dt vs. maximum end-diastolic volume (10 wk post-MI, femaleϭ359 Ϯ 58 vs. maleϭ149 Ϯ 28 mmHg ⅐ s Ϫ1 ⅐ l Ϫ1 , P Ͻ 0.05). Despite these differences, there were no differences in the heart weight to body weight ratio and infarct size between the sexes. These data demonstrate that compensatory hypertrophy is associated with an improvement in contractility and a delayed decompensation to HF in females. However, compensatory hypertrophy in males appears to be undermined by a steady decline in contractility associated with decompensation to HF. contractility; pressure-volume loops DAMAGE TO THE MYOCARDIUM FOLLOWING myocardial infarction (MI) is associated with compensatory responses such as left ventricular (LV) hypertrophy and activation of the sympathetic nervous system to maintain cardiac output. Eventually, these changes are inadequate and contractile dysfunction along with subsequent chamber dilation underlie the transition to heart failure (HF) (11, 32).There are known sex-related responses to ischemia following myocardial infarction (MI) ranging from symptoms, diagnoses, preventions, courses of disease and outcomes of existing therapies. Women have more diverse symptoms than men, which are the major causes for delayed diagnoses and treatments (18,29,37). Also, women have poorer outcomes for a number of clinical complications such as a non-Q wave MI and invasive percutaneous transluminal coronary angioplasty (16,25). Despite these sex differences in incidence, manifestation and outcome, clinical data on cardiac function changes following MI are obscured by numerous baseline differences such as age, risk factors, symptoms, and the presence of coexisting disease...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sex-related changes in cardiac function following myocardial infarction in mice

Shioura¹,

Geenen²,

Goldspink³

2008

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…97 Although ovariectomized rats do not show a decrease in phospholamban mRNA levels, estrogen replacement elicits a significant increase in expression compared with ovariectomized and sham-operated animals. 98 Similarly, the increase in Ca 2ϩ fluxes across the ryandine receptor and Na ϩ -Ca 2ϩ exchange in ovariectomized rats is reversed by estrogen treatment. 99 This latter effect of estrogen on Ca 2ϩ flux may be the result of the impact of estrogen on protein kinase A activity.…”

Section: Transgenic Models Targeting Signaling Pathwaysmentioning

confidence: 97%

The Effects of Biological Sex and Diet on the Development of Heart Failure

Konhilas

Leinwand

2007

Circulation

View full text Add to dashboard Cite

“…34 Indeed, estrogen-receptor deficient male mice also exhibit higher expression of L-type calcium channels. 35 Although Cav1.2, which mediates calcium entry into the cardiac myocyte and plays an important role in depolarization, is reduced by estrogen, the NCX, which is involved in repolarization is increased by estrogen; ovariectomy (OVX) reversed this expression pattern in females rats, 36 which is significant in light of prolonged repolarization in women. NCX mediates calcium influx and maintains the action potential plateau.…”

Section: Sexual Dimorphisms In Human and Rodent Cardiovascular Physiomentioning

confidence: 99%

The Importance of Biological Sex and Estrogen in Rodent Models of Cardiovascular Health and Disease

Blenck

Harvey

Reckelhoff

et al. 2016

Circulation Research

151

127

View full text Add to dashboard Cite

Nearly one-third of deaths in the United States are caused by cardiovascular disease (CVD) each year. In the past, CVD was thought to mainly affect men leading to the exclusion of women and female animals from clinical studies and preclinical research. In light of sexual dimorphisms in CVD, a need exists to examine baseline cardiac differences in humans and the animals used to model CVD. In humans, sex differences are apparent at every level of cardiovascular physiology from action potential duration and mitochondrial energetics to cardiac myocyte and whole heart contractile function. Biological sex is an important modifier of the development of CVD with younger women generally being protected, but this cardioprotection is lost later in life, suggesting a role for estrogen. While endogenous estrogen is most likely a mediator of the observed functional differences in both health and disease, the signaling mechanisms involved are complex and are not yet fully understood. To investigate how sex modulates CVD development, animal models are essential tools and should be useful in the development of therapeutics. This review will focus on describing the cardiovascular sexual dimorphisms that exist both physiologically as well as in common animal models of CVD.

show abstract

Effect of estrogen on calcium-handling proteins, β-adrenergic receptors, and function in rat heart

Cited by 79 publications

References 54 publications

Sex-related changes in cardiac function following myocardial infarction in mice

Sex-related changes in cardiac function following myocardial infarction in mice

The Effects of Biological Sex and Diet on the Development of Heart Failure

The Importance of Biological Sex and Estrogen in Rodent Models of Cardiovascular Health and Disease

Contact Info

Product

Resources

About