| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 NIAAA-LPS, NIH, Bethesda, Maryland, United States
2 NIAAA, NIH, Bethesda, Maryland, United States
3 Surgery, UMDNJ-New Jersey Medical School, Newark, New Jersey, United States
4 Department of Intensive Care Medicine, University Hospital, Lausanne, Lausanne, Lausanne, Switzerland
5 Scripps
6 Physiology, New York Medical College, Valhalla, New York, United States
7 Physiology, New York Medical College, Valhalla, United States
8 NIAAA, Laboratory Physiological Studies, National Institutes of Health, Bethesda, Maryland, United States
* To whom correspondence should be addressed. E-mail: pacher{at}mail.nih.gov.
Recent studies have uncovered important cross-talk between inflammation, generation of reactive oxygen and nitrogen species and lipid metabolism in the pathogenesis of cardiovascular aging. Inhibition of the endocannabinoid anandamide metabolizing enzyme, the fatty acide amide hydrolase (FAAH), is emerging as a promising novel approach for the treatment of various inflammatory disorders. In this study we have investigated the age-associated decline of cardiac function and changes in inflammatory gene expression, nitrative stress and apoptosis in FAAH knockout (FAAH-/-) mice and their wild-type (FAAH+/+) littermates. Additionally, we have explored the effects of anandamide on TNF
-induced ICAM-1 and VCAM-1 expression and monocyte-endothelial adhesion in human coronary artery endothelial cells (HCAECs). There was no difference in the cardiac function (measured by the pressure-volume conductance catheter system) between 2-3-mo-old (young) FAAH-/- and FAAH+/+ mice. In contrast, the aging-associated decline in cardiac function and increased myocardial gene expression of TNF, gp91phox, MMP-2, MMP-9, caspase 3 and 9, myocardial iNOS protein expression, nitrotyrosine formation, PARP cleavage and caspase 3/9 activity, observed in 28-31-mo-old (aging) FAAH+/+ mice, were largely attenuated in knockouts. There was no difference in the myocardial cannabinoid CB1 and CB2 receptor gene expression between young and aging FAAH-/- and FAAH+/+ mice. Anandamide dose-dependently attenuated the TNF--induced ICAM-1 and VCAM-1 expression, NF-
B activation in HCAECs, and the adhesion of monocytes to HCAECs in CB1 and CB2-dependent manner. These findings suggest that pharmacological inhibition of FAAH may represent a novel protective strategy against chronic inflammation, oxidative/nitrative stress, and apoptosis associated with cardiovascular aging and atherosclerosis.
This article has been cited by other articles:
|
|
 |
|
  K. Boengler, R. Schulz, and G. Heusch Loss of cardioprotection with ageing Cardiovasc Res, July 15, 2009; 83(2): 247 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Defer, J. Wan, R. Souktani, B. Escoubet, M. Perier, P. Caramelle, S. Manin, V. Deveaux, M.-C. Bourin, A. Zimmer, et al. The cannabinoid receptor type 2 promotes cardiac myocyte and fibroblast survival and protects against ischemia/reperfusion-induced cardiomyopathy FASEB J, July 1, 2009; 23(7): 2120 - 2130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Mukhopadhyay, M. Rajesh, S. Batkai, Y. Kashiwaya, G. Hasko, L. Liaudet, C. Szabo, and P. Pacher Role of superoxide, nitric oxide, and peroxynitrite in doxorubicin-induced cell death in vivo and in vitro Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1466 - H1483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Moezi, S. A. Gaskari, and S. S. Lee Endocannabinoids and Liver Disease. V. Endocannabinoids as mediators of vascular and cardiac abnormalities in cirrhosis Am J Physiol Gastrointest Liver Physiol, October 1, 2008; 295(4): G649 - G653. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Csiszar, N. Labinskyy, A. Podlutsky, P. M. Kaminski, M. S. Wolin, C. Zhang, P. Mukhopadhyay, P. Pacher, F. Hu, R. de Cabo, et al. Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2721 - H2735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Pacher and B. Gao Endocannabinoids and Liver Disease. III. Endocannabinoid effects on immune cells: implications for inflammatory liver diseases Am J Physiol Gastrointest Liver Physiol, April 1, 2008; 294(4): G850 - G854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Montecucco, F. Burger, F. Mach, and S. Steffens CB2 cannabinoid receptor agonist JWH-015 modulates human monocyte migration through defined intracellular signaling pathways Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1145 - H1155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Pacher and Z. Ungvari Pleiotropic effects of the CB2 cannabinoid receptor activation on human monocyte migration: implications for atherosclerosis and inflammatory diseases Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1133 - H1134. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
