Direct Relationship Between Levels of TNF-alpha Expression and Endothelial Dysfunction in Reperfusion Injury

Overview

Journal Basic Res Cardiol

Specialty Cardiology & Vascular Diseases

Date 2010 Jan 22

PMID 20091314

Citations 31

Authors

Cuihua Zhang

Junxi Wu

Xiangbin Xu

Barry J Potter

Xue Gao

Affiliations

Soon will be listed here.

Abstract

We previously found that myocardial ischemia/reperfusion (I/R) initiates expression of tumor necrosis factor-alpha (TNF) leading to coronary endothelial dysfunction. However, it is not clear whether there is a direct relationship between levels of TNF expression and endothelial dysfunction in reperfusion injury. We studied levels of TNF expression by using different transgenic animals expressing varying amounts of TNF in I/R. We crossed TNF overexpression (TNF(++/++)) with TNF knockout (TNF(-/-)) mice; thus we have a heterozygote population of mice with the expression of TNF "in between" the TNF(-/-) and TNF(++/++) mice. Mouse hearts were subjected to 30 min of global ischemia followed by 90 min of reperfusion and their vasoactivity before and after I/R was examined in wild type (WT), TNF(-/-), TNF(++/++) and TNF heterozygote (TNF(-/++), cross between TNF(-/-) and TNF(++/++)) mice. In heterozygote TNF(-/++) mice with intermediate cardiac-specific expression of TNF, acetylcholine-induced or flow-induced endothelial-dependent vasodilation following I/R was between TNF(++/++) and TNF(-/-) following I/R. Neutralizing antibodies to TNF administered immediately before the onset of reperfusion-preserved endothelial-dependent dilation following I/R in WT, TNF(-/++) and TNF(++/++) mice. In WT, TNF(-/++) and TNF(++/++) mice, I/R-induced endothelial dysfunction was progressively lessened by administration of free-radical scavenger TEMPOL immediately before initiating reperfusion. During I/R, production of superoxide (O(2) (.-)) was greatest in TNF(++/++) mice as compared to WT, TNF(-/++) and TNF(-/-) mice. Following I/R, arginase mRNA expression was elevated in the WT, substantially elevated in the TNF(-/++) and TNF(++/++) mice and not affected in the TNF(-/-) mice. These results suggest that the level of TNF expression determines arginase expression in endothelial cells during myocardial I/R, which is one of the mechanisms by which TNF compromises coronary endothelial function in reperfusion injury.

Citing Articles

Low Caloric Intake Confers Cardiovascular Protection and Improves Functional Capacity Without Affecting Immunological Response in Sedentary Older Adults.

Moura-Maia M, Brill B, Paula-Vieira R, Ramos-Gomes N, Melamed D, Silva-Reis A Nutrients. 2024; 16(21).

PMID: 39519510 PMC: 11547299. DOI: 10.3390/nu16213677.

DOES GALLIC ACID HAVE A POTENTIAL REMEDIAL EFFECT IN EXPERIMENTAL CORROSIVE BURN INJURY TO THE ESOPHAGUS?.

Basuguy E, Ozkorkmaz E Acta Clin Croat. 2024; 62(3):437-446.

PMID: 39310681 PMC: 11414001. DOI: 10.20471/acc.2023.62.03.5.

Examination of cardiac functions during acute attack and remission period in children with familial Mediterranean fever.

Gunay Y, Karagozlu F, Gemici S, Yilmaz S, Sahin S, Barut K Eur J Pediatr. 2024; 183(7):3137-3145.

PMID: 38668795 PMC: 11192814. DOI: 10.1007/s00431-024-05570-y.

Extracellular vesicles in cardiovascular disease: Biological functions and therapeutic implications.

Han C, Yang J, Sun J, Qin G Pharmacol Ther. 2021; 233:108025.

PMID: 34687770 PMC: 9018895. DOI: 10.1016/j.pharmthera.2021.108025.

Minimizing Ischemia Reperfusion Injury in Xenotransplantation.

Patel P, Connolly M, Coe T, Calhoun A, Pollok F, Markmann J Front Immunol. 2021; 12:681504.

PMID: 34566955 PMC: 8458821. DOI: 10.3389/fimmu.2021.681504.

References

Schulz R, Heusch G . Tumor necrosis factor-alpha and its receptors 1 and 2: Yin and Yang in myocardial infarction?. Circulation. 2009; 119(10):1355-7. DOI: 10.1161/CIRCULATIONAHA.108.846105. View

Thielmann M, Dorge H, Martin C, Belosjorow S, Schwanke U, van de Sand A . Myocardial dysfunction with coronary microembolization: signal transduction through a sequence of nitric oxide, tumor necrosis factor-alpha, and sphingosine. Circ Res. 2002; 90(7):807-13. DOI: 10.1161/01.res.0000014451.75415.36. View

Gao X, Zhang H, Belmadani S, Wu J, Xu X, Elford H . Role of TNF-alpha-induced reactive oxygen species in endothelial dysfunction during reperfusion injury. Am J Physiol Heart Circ Physiol. 2008; 295(6):H2242-9. PMC: 2614540. DOI: 10.1152/ajpheart.00587.2008. View

Ammar Jr R, Gutterman D, Brooks L, Dellsperger K . Free radicals mediate endothelial dysfunction of coronary arterioles in diabetes. Cardiovasc Res. 2000; 47(3):595-601. DOI: 10.1016/s0008-6363(00)00094-8. View

Weyrich A, Ma X, Lefer A . The role of L-arginine in ameliorating reperfusion injury after myocardial ischemia in the cat. Circulation. 1992; 86(1):279-88. DOI: 10.1161/01.cir.86.1.279. View

Chandrasekar B, Colston J, Freeman G . Induction of proinflammatory cytokine and antioxidant enzyme gene expression following brief myocardial ischaemia. Clin Exp Immunol. 1997; 108(2):346-51. PMC: 1904669. DOI: 10.1046/j.1365-2249.1997.d01-1017.x. View

Yang J, Park Y, Zhang H, Xu X, Laine G, Dellsperger K . Feed-forward signaling of TNF-alpha and NF-kappaB via IKK-beta pathway contributes to insulin resistance and coronary arteriolar dysfunction in type 2 diabetic mice. Am J Physiol Heart Circ Physiol. 2009; 296(6):H1850-8. PMC: 2716110. DOI: 10.1152/ajpheart.01199.2008. View

Dorge H, Schulz R, Belosjorow S, Post H, van de Sand A, Konietzka I . Coronary microembolization: the role of TNF-alpha in contractile dysfunction. J Mol Cell Cardiol. 2002; 34(1):51-62. DOI: 10.1006/jmcc.2001.1489. View

Kupatt C, Habazettl H, Goedecke A, Wolf D, Zahler S, Boekstegers P . Tumor necrosis factor-alpha contributes to ischemia- and reperfusion-induced endothelial activation in isolated hearts. Circ Res. 1999; 84(4):392-400. DOI: 10.1161/01.res.84.4.392. View

10.

Zhang C, Xu X, Potter B, Wang W, Kuo L, Michael L . TNF-alpha contributes to endothelial dysfunction in ischemia/reperfusion injury. Arterioscler Thromb Vasc Biol. 2005; 26(3):475-80. DOI: 10.1161/01.ATV.0000201932.32678.7e. View

11.

Zhang C . The role of inflammatory cytokines in endothelial dysfunction. Basic Res Cardiol. 2008; 103(5):398-406. PMC: 2705866. DOI: 10.1007/s00395-008-0733-0. View

12.

Tracey K, Beutler B, Lowry S, Merryweather J, Wolpe S, Milsark I . Shock and tissue injury induced by recombinant human cachectin. Science. 1986; 234(4775):470-4. DOI: 10.1126/science.3764421. View

13.

Gurevitch J, Frolkis I, Yuhas Y, Lifschitz-Mercer B, Berger E, Paz Y . Anti-tumor necrosis factor-alpha improves myocardial recovery after ischemia and reperfusion. J Am Coll Cardiol. 1997; 30(6):1554-61. DOI: 10.1016/s0735-1097(97)00328-8. View

14.

Schmidt A, Geigenmuller S, Volker W, Buddecke E . The antiatherogenic and antiinflammatory effect of HDL-associated lysosphingolipids operates via Akt -->NF-kappaB signalling pathways in human vascular endothelial cells. Basic Res Cardiol. 2006; 101(2):109-16. DOI: 10.1007/s00395-005-0582-z. View

15.

Lefer A, Tsao P, Ma X . Shock- and ischemia-induced mechanisms of impairment of endothelium-mediated vasodilation. Chest. 1991; 100(3 Suppl):160S-163S. View

16.

Garcia S, Pomblum V, Gams E, Langenbach M, Schipke J . Independency of myocardial stunning of endothelial stunning?. Basic Res Cardiol. 2007; 102(4):359-67. DOI: 10.1007/s00395-007-0657-0. View

17.

Oral H, Dorn 2nd G, Mann D . Sphingosine mediates the immediate negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian cardiac myocyte. J Biol Chem. 1997; 272(8):4836-42. DOI: 10.1074/jbc.272.8.4836. View

18.

Zhang D, Yi F, Zou A, Li P . Role of ceramide in TNF-alpha-induced impairment of endothelium-dependent vasorelaxation in coronary arteries. Am J Physiol Heart Circ Physiol. 2002; 283(5):H1785-94. DOI: 10.1152/ajpheart.00318.2002. View

19.

Huber S, Feldman A, Sartini D . Coxsackievirus B3 induces T regulatory cells, which inhibit cardiomyopathy in tumor necrosis factor-alpha transgenic mice. Circ Res. 2006; 99(10):1109-16. DOI: 10.1161/01.RES.0000249405.13536.49. View

20.

Tiefenbacher C, Chilian W, Mitchell M, DeFily D . Restoration of endothelium-dependent vasodilation after reperfusion injury by tetrahydrobiopterin. Circulation. 1996; 94(6):1423-9. DOI: 10.1161/01.cir.94.6.1423. View