Bone morphogenetic protein receptor type II deficiency and increased inflammatory cytokine production. A gateway to pulmonary arterial hypertension.

摘要: Rationale: Mutations in bone morphogenetic protein receptor type II (BMPR-II) underlie most cases of heritable pulmonary arterial hypertension (PAH). However, disease penetrance is only 20–30%, suggesting a requirement for additional triggers. Inflammation emerging as key disease-related factor PAH, but to date there no clear mechanism linking BMPR-II deficiency and inflammation.Objectives: To establish direct link between deficiency, consequentially heightened inflammatory response, development PAH.Methods: We used artery smooth muscle cells from Bmpr2+/− mice patients with BMPR2 mutations compared them wild-type controls. For the vivo model, we heterozygous null allele Bmpr2 (Bmpr2+/−) littermates.Measurements Main Results: Acute exposure LPS increased lung circulating IL-6 KC (IL-8 analog) levels greater extent than Similarly, muscl...