Abstract
Hypoxia has been shown to activate the pleiotropic cytokine TNFα in the lung. TNFα in turn, is known to induce pulmonary vasoconstriction. Additional effects of this cytokine in hypoxia mediated cardiopulmonary remodeling are poorly understood. To further evaluate the role of TNFα in chronic hypoxia we exposed TNFα null (TNFα–/–) and wild-type mice to three weeks of hypobaric hypoxia (10% O2). Equivalent erythocytosis (Hematocrit increased by ≥ 40%) developed in both genetic backgrounds. In contrast, right ventricular systolic pressure increased in response to three weeks of hypoxia in the wild-type mice (≥ 75%), yet was unaltered in the TNFα–/– mice. Concomitantly right ventricular hypertrophy was attenuated in the TNFα–/– mice (35 ± 5% increase) when compared to wild-type mice (124 ± 6% increase p < 0.001, n ≥ 20). Interestingly in both strains the lung wet weights increased to a similar degree in response to hypoxia. In conclusion, our data demonstrate that TNFα is an integral autocoid in chronic hypoxia mediated right ventricular hypertrophy. Moreover, additional components of cardiopulmonary remodeling may be regulated by TNFα signaling as suggested by the negligible right ventricular systolic pressure response to hypoxia in the absence of TNFα.
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Smith, R.M., McCarthy, J. & Sack, M.N. TNF alpha is required for hypoxia-mediated right ventricular hypertrophy. Mol Cell Biochem 219, 139–143 (2001). https://doi.org/10.1023/A:1010811414206
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DOI: https://doi.org/10.1023/A:1010811414206