Pharmacological activation of estrogenic receptor G protein-coupled receptor 30 attenuates angiotensin II-induced atrial fibrosis in ovariectomized mice by modulating TGF-β1/smad pathway

Li, Da; Zhan, Yinge; Ono, Katsushige; Yin, Yajuan; Wang, Le; Wei, Mei; Ji, Lishuang; Liu, Mei; Liu, Gang; Zhou, Xin; Zheng, Mingqi

doi:10.1007/s11033-022-07444-8

Cited by 5 publications

(3 citation statements)

References 32 publications

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“…The fewer ischemic areas observed in our early ERT group, may be attributed to the cardioprotective role of estradiol. In support of our results Liu et al [64] showed that the activation of GPER can attenuate fibrosis and the inflammatory response by inhibiting the TGFβ/SMAD2/3 pathway and apoptosis through Bax inhibition and Bcl2 stimulation. In addition, it has been shown that ovariectomy in aged rats resulted in a doubled type I/III collagen ratio and decreased activity of matrix metalloproteinase type 2 (MMP-2), effects that were reversed with ERT [65].…”

Section: Morphological Alterations In the Myocardium Due To Ovariecto...supporting

confidence: 92%

Early Estrogen Replacement Therapy Attenuates Cardiac Dysfunction Caused by Aging and Ovariectomy in Female Wistar Rats

Ramírez-Hernández,

López-Sanchez,

Lezama-Martínez

et al. 2024

Front. Biosci. (Landmark Ed)

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Background: Cardiovascular diseases (CVDs) are the leading cause of women's mortality, linked to aging and reduced estrogen during menopause. Estrogen replacement therapy (ERT) is suggested for CVDs prevention. Yet, its timing initiation remains contentious. Thus, we aimed to evaluate the effect of early and late estrogen therapy on cardiac function and lipid metabolism in ovariectomized old female Wistar rats. Methods: Fifty randomized female Wistar rats were included in 5 groups (n = 10, 18 months old): (1) Sham, (2) 10 weeks post ovariectomy (Ovx-10 w), (3) 10 weeks post Ovx + early estrogen replacement therapy (Ovx 10 w-early ERT), (4) 20 weeks post Ovx (Ovx-20 w) and ( 5) Ovx 20 w-late ERT. Three days (early ERT) or 10 weeks (late ERT) after surgery 17-β estradiol was given (5 µg/kg/day), and 10 weeks after the start of ERT, we assessed cardiac function by echocardiography, electrocardiography, and cardiac catheterization. Estradiol, cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were determined. Cardiac histology was performed with Masson's staining. Results: Ovariectomy (Ovx) increases left ventricle internal systolic diameter (0.4 vs 0.3 cm, *p = 0.020) and decreases shortening fraction (40 vs 54 %, *p = 0.030) regardless of therapy. ERT prevents the increase in left ventricle mass after 10 weeks post-Ovx and the ejection fractionreduction after 20 weeks. Lower P wave amplitudes (18.8 vs 24.2 ms, *p = 0.013) were found in the Ovx-20 w group. A longer duration of the QRS complex after 20 weeks post-Ovx with and without ERT was found (32.5 and 32.1 vs 28.3 ms, *p = 0.003; *p = 0.007). Diastolic blood pressure was higher 20 weeks post-Ovx (86 vs 76 mmHg, *p = 0.047), regardless of ERT. The left ventricle (LV) -dP/dt was decreased in Ovx groups without ERT (-750 vs -1320 mmHg, *p = 0.034). An increase in LV collagen deposition was found in the Ovx 10 w group vs Sham (9.58 vs 4.54 %, *p = 0.028). Early ERT avoids the increase in body weight, cholesterol and LDL caused by Ovx. Conclusions: Ovariectomy causes time-dependent alterations in lipid metabolism, morphology, electrical activity, and heart contractile function. Early but not late ERT prevents some of these effects.

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Section: Morphological Alterations In the Myocardium Due To Ovariecto...supporting

confidence: 92%

Early Estrogen Replacement Therapy Attenuates Cardiac Dysfunction Caused by Aging and Ovariectomy in Female Wistar Rats

Ramírez-Hernández,

López-Sanchez,

Lezama-Martínez

et al. 2024

Front. Biosci. (Landmark Ed)

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“…A transmission electron microscope was purchased from Hitachi, Ltd. TUNEL analysis software was obtained from Image Pro-Plus software (Media Cybernetics, Inc. All mice were anesthetized with an intraperitoneal injection of pentobarbital sodium (40 mg/kg) prior to surgery. Subsequently, the mice in the Ang II and AC groups were treated with Ang II (2 µg/kg/min) through osmotic minipumps for 3 weeks, as previously described (28). The minipump was subcutaneously implanted into the back of each mouse for 21 days.…”

Section: Methodsmentioning

confidence: 99%

Compound Kushen injection attenuates angiotensin II‑mediated heart failure by inhibiting the PI3K/Akt pathway

Wang

Yang

et al. 2023

Int J Mol Med

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Compound Kushen injection (CKI) is a type of traditional Chinese medicine that has previously been studied for the treatment of various types of cancer. Previous studies have reported that CKI regulates cell apoptosis by downregulating the PI3K/Akt pathway. The present study aimed to determine whether CKI alleviates heart failure (HF) by attenuating cardiomyocyte apoptosis via the inhibition of the PI3K/Akt pathway. Angiotensin II (Ang II) was used to elicit HF, and osmotic minipumps with either Ang II (2 µg/kg/day) or phosphate-buffered saline (PBS; 200 µl) were subcutaneously implanted into 6-week-old male C57BL/6 mice for 3 weeks. In addition, PBS or CKI (25 mg/kg/day) were subcutaneously infused once a day for 3 weeks. Echocardiography was used to examine hemodynamics. The myocardial injury biomarkers, cardiac troponin I and N-terminal (NT)-pro hormone B-type natriuretic peptide, were assessed using enzyme-linked immunosorbent assay. Transmission electron microscopy was used to determine the morphology of the myocardium. The rate of apoptosis was detected using TUNEL staining and flow cytometry (FCM), and the expression levels of apoptosis-related proteins were measured using western blot (WB) analysis. Moreover, H9C2 cells were treated with CKI (2 mg/ml) or LY294002 (an inhibitor of the PI3K/Akt pathway; 25 µmol/l) in combination with Ang II (1 µmol/l) for 48 h. Cell Counting Kit-8 assay, FCM and WB analysis were performed in the H9C2 cells to examine cell viability, cell cycle distribution and representative signaling proteins. It was found that CKI promoted healthy cardiac function, reduced myocardial structural damage and reduced the rate of cardiomyocyte apoptosis. CKI markedly attenuated the expression of apoptosis-related proteins in the PI3K/Akt pathway. The results of the in vitro experiments indicated that CKI promoted cardiomyocyte proliferation and inhibited apoptosis, similar to LY294002. On the whole, the present study demonstrates that CKI reduces cardiomyocyte apoptosis, promotes healthy cardiac function and attenuates Ang II-mediated HF. These ameliorative effects may be associated with the inhibition of the PI3K/Akt pathway.

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“…In cardiac fibroblasts culture, G1 inhibits Ang II-induced proliferation and apoptosis. In addition to this, in a model of Ang II-induced atrial fibrillation in OVX mice, the treatment with G1 reduces fibrosis and atrial fibrillation with alteration in the expression of proteins and genes related to apoptosis and involved in inflammation, resulting in an upregulation for mothers against decapentaplegic homolog(Smad)7 and inhibition of the TGF-β/Smad pathway [ 63 ].…”

Section: Mechanism Of Menopause-induced Hfpef and Targets For Treatmentmentioning

confidence: 99%

Heart Failure in Menopause: Treatment and New Approaches

Montagnoli

Sá

et al. 2022

IJMS

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Aging is an important risk factor for the development of heart failure (HF) and half of patients with HF have preserved ejection fraction (HFpEF) which is more common in elderly women. In general, sex differences that lead to discrepancies in risk factors and to the development of cardiovascular disease (CVD) have been attributed to the reduced level of circulating estrogen during menopause. Estrogen receptors adaptively modulate fibrotic, apoptotic, inflammatory processes and calcium homeostasis, factors that are directly involved in the HFpEF. Therefore, during menopause, estrogen depletion reduces the cardioprotection. Preclinical menopause models demonstrated that several signaling pathways and organ systems are closely involved in the development of HFpEF, including dysregulation of the renin-angiotensin system (RAS), chronic inflammatory process and alteration in the sympathetic nervous system. Thus, this review explores thealterations observed in the condition of HFpEF induced by menopause and the therapeutic targets with potential to interfere with the disease progress.

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Pharmacological activation of estrogenic receptor G protein-coupled receptor 30 attenuates angiotensin II-induced atrial fibrosis in ovariectomized mice by modulating TGF-β1/smad pathway

Cited by 5 publications

References 32 publications

Early Estrogen Replacement Therapy Attenuates Cardiac Dysfunction Caused by Aging and Ovariectomy in Female Wistar Rats

Early Estrogen Replacement Therapy Attenuates Cardiac Dysfunction Caused by Aging and Ovariectomy in Female Wistar Rats

Compound Kushen injection attenuates angiotensin II‑mediated heart failure by inhibiting the PI3K/Akt pathway

Heart Failure in Menopause: Treatment and New Approaches

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