perinatologyРоссийский вестник перинатологии и педиатрииRossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics)1027-40652500-2228Ltd. “The National Academy of Pediatric Science and Innovation”perinatology-28Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWSГенетика легочной гипертензииThe genetics of pulmonary hypertensionБрегельЛ. В.BregelL. V.

д.м.н., проф., зав. каф. педиатрии

БелозеровЮ. М.BelozerovYu. M.

д.м.н., проф., гл.н.с. отдела патологии сердечно-сосудистой системы у детей

НовиковП. В.NovikovP. V.

д.м.н., проф., рук. отделения психоневрологии и наследственных заболеваний с нарушением психики

ШкольниковаМ. А.ShkolnikovaM. A.

д.м.н., проф., директор; 

рук. Детского научно-практического Центра нарушений сердечного ритма

Иркутская государственная медицинская академия постдипломного образованияРоссияIrkutsk state medical Academy of postgraduate educationRussian FederationНаучно-исследовательский клинический институт педиатрии, МоскваРоссияResearch Clinical Institute of Pediatrics; MoscowRussian Federation2014020320165912227Copyright © Ltd. “The National Academy of Pediatric Science and Innovation”, 20162016Ltd. “The National Academy of Pediatric Science and Innovation”Ltd. “The National Academy of Pediatric Science and Innovation”https://www.ped-perinatology.ru/jour/about/submissions#copyrightNoticehttps://www.ped-perinatology.ru/jour/article/view/28

Представлен обзор данных клинических и экспериментальных исследований о генетических механизмах легочной артериальной гипертензии. К генетически обусловленным вариантам относятся идиопатическая и наследственная легочная гипертензия, а также часть случаев вторичной легочной гипертензии при врожденных пороках сердца. Рассмотрена роль полиморфизма генов BMPR2, BMPR1B, SMAD, принадлежащих к суперсемейству трансформирующего фактора роста — TGF-β, и реже встречающихся мутаций генов ACVRL1 и ENG. Мутации указанных генов встречаются у 6—18,2% больных с вторичной легочной артериальной гипертензией при врожденных пороках сердца. У больных с семейной легочной гипертензией гетерозиготными носителями мутаций BMPR2 являются 70—80% родственников. Патогенетические эффекты аномальной экспрессии BMPR2 реализуются с участием группы рецепторов ALK и семейства транскрипционных протеинов SMAD. Рассмотрены механизмы дисфункции BMPR2 и BMPR1B, сопровождающиеся пролиферацией гладкомышечных клеток легочных артериальных сосудов и активацией апоптоза эндотелиоцитов легочных капилляров.

Recent clinical and experimental studies data are considering relating to the genetic causes of pulmonary arterial hypertension (PAH). The genetic abnormalities were first identified in association with the idiopathic and familial form of PAH, and some cases of secondary PAH following congenital heart defects (CHD). Genetic polymorphism of BMPR2, SMADs, ALK1/ENG were described as a reason of TGF-β-cell signaling disturbances. These genetic abnormalities were found in 6—18,2% of the patients with PAH owing to CHD. There are 70-80% heterozygote carriers of BMPR2-gene mutation among the relatives of familial PAH patients. The effects of the abnormal BMPR2 signaling pathway develop with the participation of ALK-receptors and transcriptional SMAD-proteins. Then BMPR2 и BMPR1B dysfunction culminate in an expressed smooth cells proliferative response that occludes the pulmonary arterial lumen and increases the apoptosis of the endoteliocytes in the small pulmonary arteries. 

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The authors declare that there are no conflicts of interest present.