title: Berberine via suppression of transient receptor potential vanilloid 4 channel improves vascular stiffness in mice.
abstract: Berberine, as an alkaloid found in many Chinese herbs, improves vascular functions in patients with cardiovascular diseases. We determined the effects of berberine in hypertension and vascular ageing, and elucidated the underlying mechanisms. In isolated aortas, berberine dose-dependently elicited aortic relaxation. In cultured cells, berberine induced the relaxation of vascular smooth muscle cells (VSMCs). Overexpression of transient receptor potential vanilloid 4 (TRPV4) channel by genetic approaches abolished the berberine-induced reduction in intracellular Ca(2+) concentration in VSMCs and attenuated berberine-elicited vessel dilation in mice aortas. In deoxycorticosterone acetate (DOCA)-induced hypertensive model, treatment of mice with berberine or RN-1734, a pharmacological inhibitor of TRPV4, significantly decreased systemic blood pressure (BP) in control mice or mice infected with an adenovirus vector. However, berberine-induced effects of lowering BP were reversed by overexpressing TRPV4 in mice by infecting with adenovirus. Furthermore, long-term administration of berberine decreased mean BP and pulse BP, increased artery response to vasodilator and reduced vascular collagen content in aged mice deficient in apolipoprotein E (Apoe-KO), but not in Apoe-KO old mice with lentivirus-mediated overexpression of TRPV4 channel. In conclusion, berberine induces direct vasorelaxation to lower BP and reduces vascular stiffness in aged mice through suppression of TRPV4.
authors.affiliation: The Key Laboratory of Cardiovascular Remodelling & Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Medical School of Shandong University, Shandong, China.|Department of Physical Medicine & Rehabilitation, Qilu Hospital, Medical School of Shandong University, Shandong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Cardiovascular Remodelling & Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Medical School of Shandong University, Shandong, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.affiliation: Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, China.
authors.forename: Qi-Sheng
authors.initials: QS
authors.lastname: Peng
authors.affiliation: Department of Physical Medicine & Rehabilitation, Qilu Hospital, Medical School of Shandong University, Shandong, China.
authors.forename: Shou-Wei
authors.initials: SW
authors.lastname: Yue
authors.affiliation: The Key Laboratory of Cardiovascular Remodelling & Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Medical School of Shandong University, Shandong, China.
authors.forename: Shuang-Xi
authors.initials: SX
authors.lastname: Wang
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D009924:Organ Culture Techniques; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D059289:Vascular Stiffness / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; D001599:Berberine
keywords: ageing; berberine; blood pressure; transient receptor potential vanilloid 4; vascular smooth muscle cells; vascular stiffness