Chaowei Hu1, Kun Zuo2, Kuibao Li2, Yuanfeng Gao2, Mulei Chen2, Roumu Hu2, Ye Liu2, Hongjie Chi2, Hongjiang Wang2, Yanwen Qin1, Xiaoyan Liu3, Jiuchang Zhong2, Jun Cai4, Xinchun Yang2, Jing Li2. 1. The Key Laboratory of Upper Airway Dysfunction-Related Cardiovascular Diseases, Beijing an Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China. 2. Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China. 3. Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China. 4. Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
Abstract
AIM: Hypertension is a complicated disorder with multifactorial etiology and high heritability. Our previous work has identified L3MBTL4 as a novel susceptibility gene for the development of essential hypertension, accompanied with activation of p38/JNK. Yet, little evidence has been reported whether p38/JNK contributed directly to L3MBTL4-induced vascular remodeling and exploring the potential mechanism of L3MBTL4 in vascular smooth muscle cells (VSMCs). METHODS: We evaluated the contribution of L3MBTL4 on proliferation, migration, and phenotype changes of VSMCs and further explored the critical role of p38 and JNK signaling pathway underlying. RESULTS: In L3MBTL4 transgenic rats, we found that the elevated blood pressure, increased left ventricular hypertrophy, and thickened vascular media layer were significantly relieved by both p38 and JNK inhibitors. Meanwhile, increased cell proliferation, advanced cell cycle progression, greater migratory capability, and synthetic phenotype were observed in L3MBTL4 overexpressed VSMCs, which could be blocked by either p38 or JNK inhibitor. CONCLUSIONS: Our findings pinpointed that p38 and JNK were required for the proliferation and phenotype changes of VSMCs induced by L3MBTL4 in hypertension. These novel findings yield new insights into the genetic and biological basis of hypertension and are fundamental for further studies to explore the intervention strategies targeting L3MBTL4 and p38/JNK to counteract the progression of hypertension.
AIM: Hypertension is a complicated disorder with multifactorial etiology and high heritability. Our previous work has identified L3MBTL4 as a novel susceptibility gene for the development of essential hypertension, accompanied with activation of p38/JNK. Yet, little evidence has been reported whether p38/JNK contributed directly to L3MBTL4-induced vascular remodeling and exploring the potential mechanism of L3MBTL4 in vascular smooth muscle cells (VSMCs). METHODS: We evaluated the contribution of L3MBTL4 on proliferation, migration, and phenotype changes of VSMCs and further explored the critical role of p38 and JNK signaling pathway underlying. RESULTS: In L3MBTL4 transgenic rats, we found that the elevated blood pressure, increased left ventricular hypertrophy, and thickened vascular media layer were significantly relieved by both p38 and JNK inhibitors. Meanwhile, increased cell proliferation, advanced cell cycle progression, greater migratory capability, and synthetic phenotype were observed in L3MBTL4 overexpressed VSMCs, which could be blocked by either p38 or JNK inhibitor. CONCLUSIONS: Our findings pinpointed that p38 and JNK were required for the proliferation and phenotype changes of VSMCs induced by L3MBTL4 in hypertension. These novel findings yield new insights into the genetic and biological basis of hypertension and are fundamental for further studies to explore the intervention strategies targeting L3MBTL4 and p38/JNK to counteract the progression of hypertension.
Authors: Clara K Chow; Koon K Teo; Sumathy Rangarajan; Shofiqul Islam; Rajeev Gupta; Alvaro Avezum; Ahmad Bahonar; Jephat Chifamba; Gilles Dagenais; Rafael Diaz; Khawar Kazmi; Fernando Lanas; Li Wei; Patricio Lopez-Jaramillo; Lu Fanghong; Noor Hassim Ismail; Thandi Puoane; Annika Rosengren; Andrzej Szuba; Ahmet Temizhan; Andy Wielgosz; Rita Yusuf; Afzalhussein Yusufali; Martin McKee; Lisheng Liu; Prem Mony; Salim Yusuf Journal: JAMA Date: 2013-09-04 Impact factor: 56.272
Authors: Felix C Tanner; Helen Greutert; Christine Barandier; Karin Frischknecht; Thomas F Lüscher Journal: Hypertension Date: 2003-07-07 Impact factor: 10.190