title: Cardio Protective Effects of Lumbrokinase and Dilong on Second-Hand Smoke-Induced Apoptotic Signaling in the Heart of a Rat Model.
abstract: Exposure to second-hand tobacco smoke (SHS) has been epidemiologically linked to heart disease among non-smokers. However, the molecular mechanism behind SHS-induced cardiac disease is not well known. This study found that SD rats exposed to cigarette smoke at a dose of 10 cigarettes for 30 min twice a day for 1 month had a reduced left ventricle-to-tibia length ratio (mg/mm), increased cardiomyocyte apoptosis by TUNEL assay and a wider interstitial space by H&E staining. However, lumbrokinase and dilong both reversed the effects of SHS. Western blotting demonstrated significantly increased expression of the pro-apoptotic protein caspase-3 in the hearts of the rats exposed to SHS. Elevated protein expression levels of Fas, FADD and the apoptotic initiator activated caspase-8, a molecule in the death-receptor-dependent pathway, coupled with increased t-Bid and apoptotic initiator activated caspase-9 were found. Molecules in the mitochondria-dependent pathway, which disrupts mitochondrial membrane potential, were also found in rats exposed to SHS. These factors indicate myocardial apoptosis. However, treatment with lumbrokinase and dilong inhibited SHS-induced apoptosis. Regarding regulation of the survival pathway, we found in western blot analysis that cardiac protein expression of pAkt, Bcl2, and Bcl-xL was significantly down-regulated in rats exposed to SHS. These effects were reversed with lumbrokinase and dilong treatment. The effects of SHS on cardiomyocytes were also found to be mediated by the Fas death receptor-dependent apoptotic pathway, an unbalanced mitochondria membrane potential and decreased survival signaling. However, treatment with both lumbrokinase and dilong inhibited the effects of SHS. Our data suggest that lumbrokinase and dilong may prevent heart disease in SHS-exposed non-smokers.
authors.affiliation: Department of Healthcare Administration, Asia University, Taichung 41354, Taiwan, Republic of China.
authors.forename: Hung-En
authors.initials: HE
authors.lastname: Liao
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Armed Force Taichung General Hospital, Taichung 41168, Taiwan, Republic of China.|Department of Medicine, National Defense Medical Center, Taipei 10114, Taiwan, Republic of China.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Lai
authors.affiliation: Chinese Medicine Department, China Medical University, Beigang Hospital, Yunlin 65152, Taiwan, Republic of China.
authors.forename: Tsung-Jung
authors.initials: TJ
authors.lastname: Ho
authors.affiliation: Department of Pathology, Changhua Christian Hospital, Changhua 50006, Taiwan, Republic of China.|Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli 35664, Taiwan, Republic of China.
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Yeh
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Armed Force Taichung General Hospital, Taichung 41168, Taiwan, Republic of China.
authors.forename: Gwo-Ping
authors.initials: GP
authors.lastname: Jong
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Armed-Force, Taichung General Hospital, Taichung 41354, Taiwan, Republic of China.
authors.forename: Wu-Hsien
authors.initials: WH
authors.lastname: Kuo
authors.affiliation: Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy & Science, Tainan 71710, Taiwan, Republic of China.
authors.forename: Li-Chin
authors.initials: LC
authors.lastname: Chung
authors.affiliation: Division of Cardiology, China Medical University Hospital, Taichung 40402, Taiwan, Republic of China.
authors.forename: Pei-ying
authors.initials: PY
authors.lastname: Pai
authors.affiliation: Department of Dermatology, Taipei City Hospital, Renai Branch, Taipei 10341, Taiwan, Republic of China.
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Wen
authors.affiliation: Graduate Institute of Chinese Medical Science, China Medical University, Taichung 40402, Taiwan, Republic of China.|Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan, Republic of China.|Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan, Republic of China.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D010450:Endopeptidases / Q000494:pharmacology*; D008297:Male; D008516:Medicine, Chinese Traditional; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D009835:Oligochaeta; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D002316:Cardiotonic Agents; D014028:Tobacco Smoke Pollution; D010450:Endopeptidases; D053148:Caspase 3; C083421:lumbrokinase