The cyclic adenosine monophosphate elevating medicine, forskolin, reduces neointimal formation and atherogenesis in mice.

Abstract

Neointimal formation and atherogenesis are major vascular complications following percutaneous coronary intervention, and there is lack of pharmacological therapy. This study was aimed to examine the effect of forskolin (FSK), a cyclic adenosine monophosphate (cAMP)-elevating agent, on vascular response to angioplasty wire injury and on atherogenesis in mice. Forskolin treatment reduced neointima formation at 7 and 28 days after wire injury. Early morphometrics of the injured vessels revealed that FSK treatment enhanced endothelial repair and reduced inflammatory cell infiltration. In vitro treatment of primary aortic cells with FSK, at 3-100 μmol/L, increased endothelial cell proliferation, whereas FSK, at 30-100 μmol/L, inhibited smooth muscle cell proliferation. FSK inhibited lipopolysaccharide-induced leucocyte-endothelial interaction in vitro and in vivo. In a mouse model of atherosclerosis driven by dyslipidaemia and hypertension, FSK administration increased endothelial repair and reduced atherosclerotic plaque formation, without affecting blood pressure, plasma lipids or aortic aneurysms formation. In summary, FSK, at doses relevant to human therapeutic use, protects against neointimal hyperplasia and atherogenesis, and this is attributable to its activities on pro-endothelial repair and anti-inflammation. This study raises a potential of clinical use of FSK as an adjunct therapy to prevent restenosis and atherosclerosis after percutaneous coronary intervention.

• Authors: Huifeng Hao, Xiaoyan Ma, Hong Chen, Liyuan Zhu, Zhenyu Xu, Qiaoling Li, Chuansheng Xu, Yuze Zhang, Zekun Peng, Miao Wang
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 17 Pg. 9638-9645 (09 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 32810369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Colforsin
• Cyclic AMP

Topics

• Animals
• Aorta (drug effects, metabolism)
• Atherosclerosis (drug therapy, metabolism)
• Blood Pressure (drug effects)
• Cell Proliferation (drug effects)
• Colforsin (pharmacology)
• Cyclic AMP (metabolism)
• Disease Models, Animal
• Endothelial Cells (drug effects, metabolism)
• Endothelium (drug effects, metabolism)
• Hyperplasia (drug therapy, metabolism)
• Inflammation (drug therapy, metabolism)
• Leukocytes (drug effects, metabolism)
• Medicine (methods)
• Mice
• Mice, Inbred C57BL
• Muscle, Smooth, Vascular (drug effects, metabolism)
• Myocytes, Smooth Muscle (drug effects, metabolism)
• Neointima (drug therapy, metabolism)
• Signal Transduction (drug effects)