Inhibition of the Arp2/3 Complex Attenuates Angiotensin Ⅱ-Induced Cardiomyocyte Hypertrophy
10.13865/j.cnki.cjbmb.2025.07.1119
- VernacularTitle:抑制Arp2/3复合物改善血管紧张素Ⅱ诱导的心肌细胞肥大
- Author:
Li LING
1
;
Cong-Bin PAN
;
Lu-Xuan WAN
;
Zhuang-Zhuang YANG
;
Zhan-Hong REN
Author Information
1. 湖北科技学院药学院,湖北 咸宁 437100
- Publication Type:Journal Article
- Keywords:
cardiomyocyte hypertrophy;
Arp2/3 complex;
angiotensin Ⅱ(Ang Ⅱ);
neonatal rat prima-ry cardiomyocytes(NRCMs);
H9c2 cells
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(9):1332-1341,中插1-中插5
- CountryChina
- Language:Chinese
-
Abstract:
Pathological cardiac hypertrophy is an early and significant cardiac structural charac-teristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarged cardiomyocyte.Effective intervention targets for abnormally en-larged cardiomyocyte remain to be identified.Previous studies have shown that the cellular shape and size can be regulated by the actin related protein 2/3(Arp2/3)complex,which is an actin-binding protein complex involved in the actin nucleation and assembly.However,the roles of the Arp2/3 complex in cardiomyocyte hypertrophy remain unknown.Here our study identifies its no-vel roles in the occurrence and development of cardiomyocyte hypertrophy.We found that mRNA levels of all subunits from the Arp2/3 complex are significantly upregulated(P<0.05)in the an-giotensin II(Ang Ⅱ)-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy.Fur-ther studies showed that siRNA-directed ARPC2 silencing inhibits the reactivation of fetal genes and enlargement of cardiomyocyte area induced by Ang Ⅱ in neonatal rat primary cardiomyocytes(NRCMs)and H9c2 cells(P<0.05).In addition,the upstream activators of the Arp2/3 com-plex including SH3 protein interacting with Nck,90 kD(SPIN90)and Ras-related C3 botulinum toxin substrate 1(Rac1)/WASp family Verprolin-homologous protein-2(WAVE-2)are upregu-lated(P<0.05)in Ang Ⅱ-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy,indicating the excessive activation of the Arp2/3 complex.We further show that CK666,a specif-ic Arp2/3 complex inhibitor,prevents the reactivation of fetal genes and the enlargement of car-diomyocyte area induced by Ang Ⅱ in NRCMs and H9c2 cells(P<0.05).Our results reveal that the Arp2/3 complex plays a crucial role in Ang Ⅱ-induced cardiomyocyte hypertrophy,which is beneficial to further studies about the molecular mechanisms by which the Arp2/3 complex regu-lates pathological cardiac hypertrophy.
