Background/aims: Angiotensin II (AngII) activated cardiac fibroblasts (CFs) predominantly through AngII subtype 1a receptor (AT1aR). This study was carried out to explore the potential inhibitory effects and mechanisms of epigallocatechin gallate (EGCG) on AngII induced rat CFs.
Methods: Viability, proliferation and collagen production of CFs were measured by MTT assay, [3H]-thymidine and [3H]-proline incorporation respectively. β-arrestin1 (βarr1), AT1aR and AT1bR mRNA levels were determined by quantitative PCR. AT1R, Gq, βarr 1/2, phosphorylated kinase C (p-PKC)-delta expressions were detected by western blotting. We blocked βarr1 expression using βarr1 small interfering RNA (siRNA).
Results: EGCG inhibited the activation of CFs induced by AngII. βarr1 mRNA level revealed a positive correlation with the viability of CFs. SiRNA targeting βarr1 blocked the activation of CFs. In vitro, AngII increased βarr1 mRNA, total and membrane βarr1 protein expressions, but reduced AT1aR mRNA, global and membrane AT1R, total Gq and cytoplasmic p-PKC-delta levels. Administration of EGCG restored the above abnormalities, whereas Gq levels were not affected.
Conclusion: Our findings showed that βarr1 is essential for AngII-mediated activation of CFs. EGCG attenuated CFs activation induced by AngII via regulating βarr1 and thus, modulating AT1aR mediated signaling.
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http://dx.doi.org/10.1159/000343371 | DOI Listing |
J Frailty Aging
February 2025
Division of Experimental Medicine, McGill University, Montreal, QC Canada; Division of Cardiology, Jewish General Hospital, Montreal, QC Canada. Electronic address:
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January 2025
Department of Cardiology, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory, Disease, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, Guangdong, China.
Increased activity of acid sphingomyelinase (ASMase) has been linked to diabetes and organ fibrosis. Nevertheless, the precise influence of ASMase on diabetic myocardial fibrosis and the corresponding molecular mechanisms remain elusive. In this study, we aim to elucidate whether ASMase contributes to diabetic myocardial fibrosis through the phosphorylation mediated by MAPK, thereby culminating in the development of diabetic cardiomyopathy (DCM).
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January 2025
Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, Research Institute of Chinese Medical Clinical Foundation and Immunology, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China.
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January 2025
Division of Adolescent and Young Adult Medicine, Departments of Pediatrics, Johns Hokins University School of Medicine, 200 N. Wolfe St., Room 2077, Baltimore, MD, 21287, USA.
Background: We have noted that some adolescents and young adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) report difficulty with arms-overhead activities, suggestive of brachial plexus dysfunction or thoracic outlet syndrome (TOS). In the TOS literature, diagnostic maneuvers focus on the provocation of upper limb symptoms (arm fatigue and heaviness, paresthesias, neck and upper back pain), but not on elicitation of systemic symptoms.
Objectives: To estimate the proportion of patients with fatiguing illness who experience local and systemic symptoms during a common maneuver used in evaluating TOS-the elevated arm stress test (EAST).
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating but poorly-understood disease. ME/CFS symptoms can range from mild to severe, and include immune system effects alongside incapacitating fatigue and post-exertional disease exacerbation. In this study, we examined immunological profiles of people living with ME/CFS by flow cytometry, focusing on cytotoxic cells, to determine whether people with mild/moderate (n= 43) or severe ME/CFS (n=53) expressed different immunological markers.
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