Classic ischemic but not pharmacologic preconditioning is abrogated following genetic ablation of the TNFα gene

Smith, Robert M.; Suleman, Naushaad; McCarthy, Joy; Sack, Michael N.

doi:10.1016/s0008-6363(02)00283-3

Cited by 86 publications

(86 citation statements)

References 42 publications

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“…Although it is known that TNF-␣ acts through at least two different receptors [TNF-␣ receptor 1 and 2 (TNFR1 and TNFR2)], it is not clear which receptor(s) mediates the effects of TNF-␣ in the post-MI tissue processes of cardiac remodeling. Indeed, the effects of blocking TNF-␣ in MI remain controversial; production of MI in mice lacking expression of both TNFR1 and TNFR2 led to increased infarct sizes and myocardial apoptosis in the early post-MI period (17), whereas pre-MI neutralization (22,34) reduces infarct size. Furthermore, the reduction of ischemic injury achieved by late ischemia-reperfusion is dependent on TNF-␣ (41), whereas the role of TNF-␣ in the classical (early) preconditioning reduction of MI size remains unclear (4).…”

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confidence: 99%

Inhibition of tumor necrosis factor receptor-1-mediated pathways has beneficial effects in a murine model of postischemic remodeling

Ramani

Mathier

Wang

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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man. Inhibition of tumor necrosis factor receptor-1-mediated pathways has beneficial effects in a murine model of postischemic remodeling. Am J Physiol Heart Circ Physiol 287: H1369 -H1377, 2004; 10.1152/ajpheart.00641.2003.-The aim of the present study was to investigate the importance of tumor necrosis factor (TNF)-␣ receptor-1 (TNFR1)-mediated pathways in a murine model of myocardial infarction and remodeling. One hundred and ninety-four wild-type (WT) and TNFR1 gene-deleted (TNFR1KO) mice underwent left coronary artery ligation to induce myocardial infarction. On days 1, 3, 7, and 42, mice underwent transesophageal echocardiography. Hearts were weighed, and the left ventricle (LV) was assayed for matrix metalloproteinase (MMP)-2 and -9 activity and for tissue inhibitor of MMP (TIMP)-1 and -2 expression. Deletion of the TNFR1 gene substantially improved survival because no deaths were observed in TNFR1KO mice versus 56.4% and 18.2% in WT males and females, respectively (P Ͻ 0.002). At 42 days, LV remodeling, assessed by LV function (fractional area change of 31.9 Ϯ 7.9%, 32.2 Ϯ 7.7%, and 21.6 Ϯ 7.1% in TNFR1KO males, TNFR1KO females, and WT females, respectively, P Ͻ 0.04), and hypertrophy (heart weight-tobody weight ratios of 5.435 Ϯ 0.986, 5.485 Ϯ 0.677, and 6.726 Ϯ 0.704 mg/g, P Ͻ 0.04) were ameliorated in TNFR1KO mice. MMP-9 activity was highest at 3 days postinfarction and was highest in WT males (1.9 Ϯ 0.4 4, 3.6 Ϯ 0.24, 1.15 Ϯ 0.28, and 1.3 Ϯ 1.2 ng/100 g protein, respectively, in TNFR1KO males, WT males, TNFR1KO females, and WT females, respectively, P Ͻ 0.002), whereas at 3 days TIMP-1 mRNA fold upregulation compared with type-and sexmatched controls was lowest in WT males (138.32 Ϯ 13.05, 46.74 Ϯ 5.43, 186.09 Ϯ 28.07, and 101.76 Ϯ 22.48, respectively, P Ͻ 0.002). MMP-2 and TIMP-2 increased similarly in all infarcted groups. These findings suggest that the benefits of TNFR1 ablation might be attributable at least in part to the attenuation of cytokine-mediated imbalances in MMP-TIMP activity. extracellular matrix; left ventricular function; myocardial infarction ISCHEMIC HEART DISEASE is the major cause of congestive heart failure (CHF) in the United States. The adverse effects of left ventricular (LV) remodeling after myocardial infarction (MI) have been recognized as a primary factor in the development of ischemic cardiomyopathy and CHF (7,37,40). After the heart undergoes coronary occlusion, the infarct zone is characterized by cardiomyocyte cell death, degradation of the extracellular matrix (ECM), and neutrophil infiltration, followed by granulation tissue formation and maturation of granulation tissue into scar (6,25,30). However, remodeling also occurs in areas distant to the infarct zone and includes hypertrophy and dilatation. Recent improvements in mortality and morbidity after MI can be attributed to treatment modalities directed against late post infarction remodeling [i.e., dilation of the surviving myocardium (24)]. However, adverse outcomes, both early and late, are still common in t...

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confidence: 99%

Inhibition of tumor necrosis factor receptor-1-mediated pathways has beneficial effects in a murine model of postischemic remodeling

Ramani

Mathier

Wang

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…On the other hand, inflammatory cytokines such as TNF-␣ are also involved in triggering IP, because pretreatment with TNF-␣ antibodies abolished infarct size reduction achieved by late IP in a rat model of myocardial infarction (22), and genetic ablation of TNF-␣ abolishes infarct size reduction by classic IP in mice (19).…”

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confidence: 99%

TNF-α antibodies are as effective as ischemic preconditioning in reducing infarct size in rabbits

Belosjorow

Bolle

Duschin

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Pretreatment with tumor necrosis factor-α (TNF-α) antibodies abolishes myocardial infarct size reduction by late ischemic preconditioning (IP). Whether or not TNF-α is also important for myocardial infarct size reduction by classic IP is unknown. Anesthetized rabbits were untreated ( group 1, n = 7), classically preconditioned by 5 min left coronary artery occlusion/10 min reperfusion ( group 2, n = 6), or pretreated with TNF-α antibodies without ( group 3, n = 6) or with IP ( group 4, n = 6) before undergoing 30 min of occlusion and 180 min of reperfusion. Infarct size in group 1 was 44 ± 11 (means ± SD)% of the area at risk. With a comparable area at risk, infarct size was reduced to 13 ± 7%, 23 ± 8%, and 19 ± 12% (all P < 0.05) in groups 2, 3, and 4, respectively. The circulating TNF-α concentration was increased during ischemia in group 1 from 752 ± 403 to 1,542 ± 482 U/ml ( P < 0.05) but remained unchanged in all other groups. Circulating TNF-α concentration during ischemia and infarct size correlated in all groups ( r = 0.76). IP, TNF-α antibodies, and the combined approach reduced infarct size to a comparable extent. Therefore, the question of whether or not TNF-α is causally involved in the infarct size reduction by IP in rabbits could not be answered.

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“…TNF-α has been implicated in the development of ischemic tolerance, since this effect is not observed in TNF-α knockout mice (27). Likewise, in one study, TNF-α protected cultured neurons against ischemic death and cultured astrocytes against the proinflammatory effects of TNF-α (28).…”

Section: Discussionmentioning

confidence: 99%

“…These would reduce NO synthase induction in the inflamed bladder and the consequent increase in NO production. In addition, rIPC possibly inhibits IFO-induced inducible NO synthase by producing small amounts of NO and/or TNF-α during the reperfusion phase of IPC, especially since production of these substances has been implicated in the development of ischemic tolerance after induction of IPC (27,28,30).…”

Section: Discussionmentioning

confidence: 99%

Hind limb ischemic preconditioning induces an anti-inflammatory response by remote organs in rats

Filho

Loiola

Rocha

et al. 2009

Braz J Med Biol Res

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Classic ischemic but not pharmacologic preconditioning is abrogated following genetic ablation of the TNFα gene

Cited by 86 publications

References 42 publications

Inhibition of tumor necrosis factor receptor-1-mediated pathways has beneficial effects in a murine model of postischemic remodeling

Inhibition of tumor necrosis factor receptor-1-mediated pathways has beneficial effects in a murine model of postischemic remodeling

TNF-α antibodies are as effective as ischemic preconditioning in reducing infarct size in rabbits

Hind limb ischemic preconditioning induces an anti-inflammatory response by remote organs in rats

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