α,β-Unsaturated aldehyde crotonaldehyde triggers cardiomyocyte contractile dysfunction: role of TRPV1 and mitochondrial function.
Recent evidence has suggested that cigarette smoking is associated with an increased prevalence of heart diseases. Given that cigarette smoking triggers proinflammatory response via stimulation of the capsaicin-sensitive transient receptor potential cation channel TRPV1, this study was designed to evaluate the effect of an essential α,β-unsaturated aldehyde from cigarette smoke crotonaldehyde on myocardial function and the underlying mechanism with a focus on TRPV1 and mitochondria. Cardiomyocyte mechanical and intracellular Ca2+ properties were evaluated including peak shortening (PS), maximal velocity of shortening/relengthening (±dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR90), fura-2 fluorescence intensity (FFI), intracellular Ca2+ decay and SERCA activity. Apoptosis and TRPV1 were evaluated using Western blot analysis. Production of reactive oxygen species (ROS) and DNA damage were measured using the intracellular fluoroprobe 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate and 8-hydroxy-2'-deoxyguanosine (8-OHdG), respectively. Our data revealed that crotonaldehyde interrupted cardiomyocyte contractile and intracellular Ca2+ property including depressed PS, ±dL/dt, ΔFFI and SERCA activity, as well as prolonged TR90 and intracellular Ca2+ decay. Crotonaldehyde exposure increased TRPV1 and NADPH oxidase levels, promoted apoptosis, mitochondrial injury (decreased aconitase activity, PGC-1α and UCP-2) as well as production of ROS and 8-OHdG. Interestingly, crotonaldehyde-induced cardiac defect was obliterated by the ROS scavenger glutathione and the TRPV1 inhibitor capsazepine. Capsazepine (not glutathione) ablated crotonaldehyde-induced mitochondrial damage. Capsazepine, glutathione and the NADPH inhibitor apocynin negated crotonaldehyde-induced ROS accumulation. Our data suggest a role of crotonaldehyde compromises cardiomyocyte mechanical function possibly through a TRPV1- and mitochondria-dependent oxidative stress mechanism.
Department of Cardiology, The Third Hospital of Nanchang, Nanchang, Jiangxi 330009, China.
Zhaohui
Z
Pei
Department of Rehabilitation Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
Zhiqiang
Z
Zhuang
Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China; Department of Clinical Pharmacology, Bethune International Peace Hospital of People's Liberation Army, Shijiazhuang, Hebei 050082, China.
Hanfei
H
Sang
Department of Clinical Immunology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Zhenbiao
Z
Wu
Department of Cardiology, The Second People's Hospital of Guangdong Province, Guangzhou, Guangdong 511442, China.
Rongsen
R
Meng
Department of Clinical Immunology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China; University of Wyoming College of Health Sciences, Laramie, WY 82071, USA.
Emily Y
EY
He
University of Wyoming College of Health Sciences, Laramie, WY 82071, USA.
Glenda I
GI
Scott
University of Wyoming College of Health Sciences, Laramie, WY 82071, USA.
Jackie R
JR
Maris
Department of Gynecology and Obstetrics, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 511442, China. Electronic address: hqyylrm@126.com.
Ruiman
R
Li
University of Wyoming College of Health Sciences, Laramie, WY 82071, USA. Electronic address: jren@uwyo.edu.
Jun
J
Ren
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000154:Aconitate Hydratase / Q000378:metabolism; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D012907:Smoking; D050916:TRPV Cation Channels / Q000378:metabolism*
D000447:Aldehydes; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D000080242:8-Hydroxy-2'-Deoxyguanosine; C012796:2-butenal; D053148:Caspase 3; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000154:Aconitate Hydratase; D003849:Deoxyguanosine; D002118:Calcium
Cardiomyocytes; Contractile function; Crotonaldehyde; Oxidative stress; TRPV1