PMID- 28758430 OWN - NLM STAT- MEDLINE DCOM- 20180727 LR - 20180727 IS - 1205-7541 (Electronic) IS - 0008-4212 (Linking) VI - 96 IP - 1 DP - 2018 Jan TI - Calpain inhibitor I attenuates atherosclerosis and inflammation in atherosclerotic rats through eNOS/NO/NF-kappaB pathway. PG - 60-67 LID - 10.1139/cjpp-2016-0652 [doi] AB - We previously reported that calpain, the Ca(2+)-sensitive cysteine protease, gets involved in atherogenesis. This study aimed to investigate the effects of calpain inhibitor I (CAI, 5 mg/kg per day) with or without N(G)-nitro-l-arginine-methyl ester (l-NAME) (100 mg/kg per day), the inhibitor of nitric oxide synthase (NOS), on atherosclerosis and inflammation in a rat model induced by high-cholesterol diet (HCD). The results demonstrated HCD increased protein expression of calpain-1 but not calpain-2 in aortic tissue. In addition, CAI reduced the thickness of atherosclerotic intima compared with HCD group, which was weakened by the l-NAME combination. CAI with or without l-NAME decreased the activity of calpain in the aorta. Also, CAI decreased the expressions of vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) in the aorta at the levels of both mRNA and protein. Furthermore, CAI increased the activity and the protein expression of endothelial NOS (eNOS) accompanied by increased content of NO and downregulated the protein expression of nuclear factor kappaB (NF-kappaB) of the nucleus in the aorta. However, the abovementioned effects were at least partly cancelled by l-NAME except for the protein expression of eNOS. The results suggested that CAI attenuated atherosclerosis and inflammation through eNOS/NO/NF-kappaB pathway. FAU - Yu, Lan AU - Yu L AD - a Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China. AD - b Central Hospital of Yingkou Development Areas, Yingkou 115007, China. FAU - Yin, Meihui AU - Yin M AD - a Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China. FAU - Yang, Xueyan AU - Yang X AD - a Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China. AD - c Internal Medicine-Cardiovascular Departments, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China. FAU - Lu, Meili AU - Lu M AD - a Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China. FAU - Tang, Futian AU - Tang F AD - a Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China. FAU - Wang, Hongxin AU - Wang H AD - a Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China. LA - eng PT - Journal Article DEP - 20170730 PL - Canada TA - Can J Physiol Pharmacol JT - Canadian journal of physiology and pharmacology JID - 0372712 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (CD68 antigen, human) RN - 0 (Chemokine CCL2) RN - 0 (Glycoproteins) RN - 0 (Lipids) RN - 0 (NF-kappa B) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 0 (calpain inhibitors) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) RN - EC 3.4.22.- (Calpain) SB - IM MH - Animals MH - Antigens, CD/metabolism MH - Antigens, Differentiation, Myelomonocytic/metabolism MH - Aorta/drug effects/enzymology MH - Atherosclerosis/blood/complications/*drug therapy/*metabolism MH - Calpain/metabolism MH - Cell Nucleus/drug effects/metabolism MH - Chemokine CCL2/metabolism MH - Glycoproteins/pharmacology/*therapeutic use MH - Inflammation/blood/complications/*drug therapy/*metabolism MH - Intercellular Adhesion Molecule-1/metabolism MH - Lipids/blood MH - Male MH - NF-kappa B/*metabolism MH - Nitric Oxide/*metabolism MH - Nitric Oxide Synthase Type III/*metabolism MH - Protein Transport/drug effects MH - Rats, Sprague-Dawley MH - Signal Transduction/drug effects MH - Vascular Cell Adhesion Molecule-1/metabolism OTO - NOTNLM OT - NF-kappaB OT - atherosclerosis OT - atherosclerose OT - calpain inhibitor CAI OT - endothelial nitric oxide synthase OT - inhibiteur de la calpaine ICA OT - nitric oxide OT - oxyde nitrique OT - oxyde nitrique synthase endotheliale EDAT- 2017/08/02 06:00 MHDA- 2018/07/28 06:00 CRDT- 2017/08/01 06:00 PHST- 2017/08/02 06:00 [pubmed] PHST- 2018/07/28 06:00 [medline] PHST- 2017/08/01 06:00 [entrez] AID - 10.1139/cjpp-2016-0652 [doi] PST - ppublish SO - Can J Physiol Pharmacol. 2018 Jan;96(1):60-67. doi: 10.1139/cjpp-2016-0652. Epub 2017 Jul 30.