Tags

Type your tag names separated by a space and hit enter

Cardiac-specific overexpression of metallothionein rescues nicotine-induced cardiac contractile dysfunction and interstitial fibrosis.
Toxicol Lett. 2011 Apr 10; 202(1):8-14.TL

Abstract

Cigarette smoking is a devastating risk factor for cardiovascular diseases and nicotine is believed the main toxin component responsible for the toxic myocardial effects of smoking. Nonetheless, neither the precise mechanism of nicotine-induced cardiac dysfunction nor effective treatment is elucidated. The aim of this study was to evaluate the impact of cardiac-specific overexpression of heavy metal scavenger metallothionein on myocardial geometry and mechanical function following nicotine exposure. Adult male friend virus B (FVB) wild-type and metallothionein mice were injected with nicotine (2 mg/kg/d) intraperitoneally for 10 days. Mechanical and intracellular Ca²+ properties were examined. Myocardial histology (cross-sectional area and fibrosis) was evaluated by hematoxylin and eosin (H&E) and Masson trichrome staining, respectively. Oxidative stress and apoptosis were measured by fluoroprobe 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H₂DCFDA) fluorescence and caspase-3 activity, respectively. Nicotine exposure failed to affect the protein abundance of metallothionein. Our data revealed reduced echocardiographic contractile capacity (fractional shortening), altered cardiomyocyte contractile and intracellular Ca²+ properties including depressed peak shortening amplitude, maximal velocity of shortening/relengthening, resting and electrically-stimulated rise in intracellular Ca²+, as well as prolonged duration of relengthening and intracellular Ca²+ clearance in hearts from nicotine-treated FVB mice, the effect of which was ameliorated by metallothionein. Biochemical and histological findings depicted overt accumulation of reactive oxygen species (ROS), apoptosis and myocardial fibrosis without any change in myocardial cross-sectional area following nicotine treatment, which was mitigated by metallothionein. Taken together, our findings suggest the antioxidant metallothionein may reconcile short-term nicotine exposure-induced myocardial contractile dysfunction and fibrosis possibly through inhibition of ROS accumulation and apoptosis.

Authors+Show Affiliations

Department of Biological Pharmacy, Agricultural University of Hebei College of Life Sciences, Baoding 071001, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21238558

Citation

Hu, Nan, et al. "Cardiac-specific Overexpression of Metallothionein Rescues Nicotine-induced Cardiac Contractile Dysfunction and Interstitial Fibrosis." Toxicology Letters, vol. 202, no. 1, 2011, pp. 8-14.
Hu N, Guo R, Han X, et al. Cardiac-specific overexpression of metallothionein rescues nicotine-induced cardiac contractile dysfunction and interstitial fibrosis. Toxicol Lett. 2011;202(1):8-14.
Hu, N., Guo, R., Han, X., Zhu, B., & Ren, J. (2011). Cardiac-specific overexpression of metallothionein rescues nicotine-induced cardiac contractile dysfunction and interstitial fibrosis. Toxicology Letters, 202(1), 8-14. https://doi.org/10.1016/j.toxlet.2011.01.007
Hu N, et al. Cardiac-specific Overexpression of Metallothionein Rescues Nicotine-induced Cardiac Contractile Dysfunction and Interstitial Fibrosis. Toxicol Lett. 2011 Apr 10;202(1):8-14. PubMed PMID: 21238558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiac-specific overexpression of metallothionein rescues nicotine-induced cardiac contractile dysfunction and interstitial fibrosis. AU - Hu,Nan, AU - Guo,Rui, AU - Han,Xuefeng, AU - Zhu,Baocheng, AU - Ren,Jun, Y1 - 2011/01/14/ PY - 2010/10/28/received PY - 2011/01/07/revised PY - 2011/01/07/accepted PY - 2011/1/18/entrez PY - 2011/1/18/pubmed PY - 2011/4/19/medline SP - 8 EP - 14 JF - Toxicology letters JO - Toxicol. Lett. VL - 202 IS - 1 N2 - Cigarette smoking is a devastating risk factor for cardiovascular diseases and nicotine is believed the main toxin component responsible for the toxic myocardial effects of smoking. Nonetheless, neither the precise mechanism of nicotine-induced cardiac dysfunction nor effective treatment is elucidated. The aim of this study was to evaluate the impact of cardiac-specific overexpression of heavy metal scavenger metallothionein on myocardial geometry and mechanical function following nicotine exposure. Adult male friend virus B (FVB) wild-type and metallothionein mice were injected with nicotine (2 mg/kg/d) intraperitoneally for 10 days. Mechanical and intracellular Ca²+ properties were examined. Myocardial histology (cross-sectional area and fibrosis) was evaluated by hematoxylin and eosin (H&E) and Masson trichrome staining, respectively. Oxidative stress and apoptosis were measured by fluoroprobe 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H₂DCFDA) fluorescence and caspase-3 activity, respectively. Nicotine exposure failed to affect the protein abundance of metallothionein. Our data revealed reduced echocardiographic contractile capacity (fractional shortening), altered cardiomyocyte contractile and intracellular Ca²+ properties including depressed peak shortening amplitude, maximal velocity of shortening/relengthening, resting and electrically-stimulated rise in intracellular Ca²+, as well as prolonged duration of relengthening and intracellular Ca²+ clearance in hearts from nicotine-treated FVB mice, the effect of which was ameliorated by metallothionein. Biochemical and histological findings depicted overt accumulation of reactive oxygen species (ROS), apoptosis and myocardial fibrosis without any change in myocardial cross-sectional area following nicotine treatment, which was mitigated by metallothionein. Taken together, our findings suggest the antioxidant metallothionein may reconcile short-term nicotine exposure-induced myocardial contractile dysfunction and fibrosis possibly through inhibition of ROS accumulation and apoptosis. SN - 1879-3169 UR - https://www.unboundmedicine.com/medline/citation/21238558/Cardiac_specific_overexpression_of_metallothionein_rescues_nicotine_induced_cardiac_contractile_dysfunction_and_interstitial_fibrosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-4274(11)00009-9 DB - PRIME DP - Unbound Medicine ER -