Species differences exist in the regulation of pulmonary artery smooth muscle cell proliferation, with COX-2 mediating inhibition in humans and iNOS in rats, highlighting potential therapeutic targets for pulmonary hypertension.
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Species differences limit rodent-to-human extrapolation for PA SMC regulation; leaves open species-specific PH targets.
Pulmonary hypertension is characterized by hypertrophy and hyperplasia of vascular smooth muscle occurring via an unknown mechanism. Cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) are expressed under inflammatory conditions and produce mediators that regulate growth in some tissues. We have therefore addressed the question of COX-2 and iNOS involvement in proliferation of human and rat pulmonary artery (PA) smooth-muscle cells (SMC). Interleukin (IL)-1beta suppressed proliferation of both human and rat PA SMC. Moreover, IL-1beta induced COX-2 expression in both cell types. By contrast, IL-1beta stimulated the expression of iNOS protein in rat cells only. COX-2 induced in human cells inhibited proliferation, whereas COX-2 products in rat cells were without affect. However, iNOS activity in rat cells suppressed their proliferation. We conclude that human and rat evolution has diverged such that COX-2 and iNOS, although induced by the same mediator, have different levels of activity and functions in the two species. In humans, induction of COX-2 during pulmonary hypertension may be beneficial for long-term treatment of this disease.
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Jourdan et al. (1999) studied this question.
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