title: Molecular and cellular mechanisms of cigarette smoke-induced myocardial injury: prevention by vitamin C.
abstract: BACKGROUND
  Cardiovascular disease (CVD) remains one of the major killers in modern society. One strong risk factor of CVD is cigarette smoking that causes myocardial injury and leads to the genesis of pathological cardiovascular events. However, the exact toxic component(s) of cigarette smoke (CS) and its molecular and cellular mechanisms for causing myocardial injury leading to heart damage and its prevention are largely unknown.
  
  
  RESULTS
  Using a guinea pig model, here we show that chronic exposure to CS produces myocardial injury that is prevented by vitamin C. Male guinea pigs were fed either vitamin C-deficient (0.5 mg/day) or vitamin C-sufficient (15 mg/day) diet and subjected to CS exposure from 5 Kentucky Research cigarettes (3R4F)/day (6 days/week) in a smoke chamber up to 8 weeks. Pair-fed sham controls were subjected to air exposure instead of CS exposure under similar conditions. Myocardial injury was produced in CS-exposed marginal vitamin C-deficient guinea pigs as evidenced by release of cardiac Troponin-T and I in the serum, oxidative stress, inflammation, apoptosis, thrombosis and collagen deposition in the myocardium. Treatment of rat cardiomyocyte cells (H9c2) in vitro and guinea pigs in vivo with p-benzoquinone (p-BQ) in amounts derived from CS revealed that p-BQ was a major factor responsible for CS-induced myocardial damage. A moderately large dose of vitamin C (15 mg/day) prevented CS/p-BQ-induced myocardial injury. Population based studies indicated that plasma vitamin C levels of smokers without disease were significantly lower (p = 0,0000) than that of non-smokers. Vitamin C levels of CS-related cardiovascular patients were further lower (p = 0.0000) than that of smokers without disease.
  
  
  CONCLUSIONS
  The results indicate that dietary supplementation of vitamin C may be a novel and simple therapy for the prevention of pathological cardiovascular events in habitual smokers.
authors.affiliation: Department of Biotechnology, DrBC Guha Centre for Genetic Engineering and Biotechnology, Calcutta University College of Science, Kolkata, India.
authors.forename: Archita
authors.initials: A
authors.lastname: Das
authors.forename: Neekkan
authors.initials: N
authors.lastname: Dey
authors.forename: Arunava
authors.initials: A
authors.lastname: Ghosh
authors.forename: Shovanendu
authors.initials: S
authors.lastname: Das
authors.forename: Dhruba J
authors.initials: DJ
authors.lastname: Chattopadhyay
authors.forename: Indu B
authors.initials: IB
authors.lastname: Chatterjee
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D016227:Benzoquinones / Q000378:metabolism; D018450:Disease Progression; D004789:Enzyme Activation / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy / Q000473:pathology* / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D012907:Smoking / Q000009:adverse effects*
chemical_list: D016227:Benzoquinones; C004532:quinone; D020782:Matrix Metalloproteinases; D001205:Ascorbic Acid