What is the clinical evidence from this study?

Study design: Other. Population: Chronic stress-induced cardiomyopathy. Intervention: Estradiol (E2) vs. Placebo (olive oil) / Ovariectomy without E2. Primary outcome: Macrophage polarization and cardiac function.

What does this research mean for the field?

Estrogen attenuates chronic stress-induced cardiomyopathy by preventing excessive β2-adrenergic receptor depletion and promoting macrophage polarization from a pro-inflammatory CD86+ to an anti-inflammatory CD206+ phenotype. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

September 28, 2021Frontiers in Cell and Developmental BiologyOpen Access

Estrogen Attenuates Chronic Stress-Induced Cardiomyopathy by Adaptively Regulating Macrophage Polarizations via β2-Adrenergic Receptor Modulation

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Key result

Estrogen attenuates stress-induced cardiomyopathy by preserving β2-adrenergic receptors and promoting anti-inflammatory macrophages.

Why the study?

Postmenopausal women are predisposed to chronic stress-induced cardiomyopathy, and researchers sought to determine whether estrogen modulates the macrophage β2AR-Gs/Gi pathway to confer cardioprotection during stress.

Population

Female Sprague-Dawley rats and peritoneal macrophages from wild-type and β2AR-knockout female mice

Comparison

Estradiol vs vehicle or β2AR blocker under isoproterenol stress after ovariectomy or sham surgery

Design

Preclinical in vivo and in vitro experimental study

Authors

HHHongjian HouShangqiu Normal University GAGabriel Komla AdzikaUniversity of Pennsylvania QWQi WuShanghai University

Discussion

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Implication

Hypothesis-generating for estrogen in stress cardiomyopathy; leaves open human translation pending clinical trials.

Structured PICO

Population

Adult female Sprague-Dawley rats and FVB mice subjected to ovariectomy and isoproterenol-induced chronic stress to evaluate the cardioprotective and immunomodulatory effects of estrogen.

Intervention

Estradiol (E2) 40 μg/kg/day injected 2 weeks after OVX, followed by chronic stress induction with isoproterenol (ISO) 5 mg/kg/day on day 36. In vitro: E2, ISO, and β2AR blocker ICI 118,551.

Comparator

OVX without E2 (E2 deficiency), Sham operations, or β2AR inhibition.

Outcome

Cardiac function indexes (LVSP, LVEDP, + dp/dt and −dp/dt), myocardial architecture (cardiomyocyte diameter and fibrosis), β2AR alterations, and macrophage (CD86+ and CD206+) infiltrations.surrogate

Estrogen confers cardioprotection against chronic stress-induced cardiomyopathy by promoting adaptive immunomodulation of macrophage phenotypes via β2-adrenergic receptor-mediated signaling.

Limitations

The role of β1-adrenergic receptors in immunologic functions facilitated by E2 was not elucidated.
Exogenous E2 did not confer anti-inflammatory effects as potently as endogenous E2, possibly due to the absence of other ovarian secretions like progesterone.
Constant exogenous E2 dosage did not mimic the natural estrous cycle fluctuations of endogenous E2, which may account for slight variations in efficacy.

Cite This Study

Hou et al. (2021) studied Chronic stress-induced cardiomyopathy. Estradiol (E2) vs. Placebo (olive oil) / Ovariectomy without E2 was evaluated on Macrophage polarization and cardiac function. Estrogen attenuated chronic stress-induced cardiomyopathy by preventing excessive depletion of β2-adrenergic receptors and enhancing the polarization of macrophages from a pro-inflammatory CD86+ to an anti-inflammatory CD206+ phenotype.

synapsesocial.com/papers/6aa5334446e2dc2162921924 https://doi.org/10.3389/fcell.2021.737003

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Estrogen Attenuates Chronic Stress-Induced Cardiomyopathy by Adaptively Regulating Macrophage Polarizations via β2-Adrenergic Receptor Modulation

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Estrogen Attenuates Chronic Stress-Induced Cardiomyopathy by Adaptively Regulating Macrophage Polarizations via β2-Adrenergic Receptor Modulation

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Also Consider

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