Matches in SemOpenAlex for { <https://semopenalex.org/work/W2756682806> ?p ?o ?g. }
- W2756682806 endingPage "1935" @default.
- W2756682806 startingPage "1920" @default.
- W2756682806 abstract "Immune dysregulation has been linked to occlusive vascular remodeling in pulmonary arterial hypertension (PAH) that is hereditary, idiopathic, or associated with other conditions. Circulating autoantibodies, lung perivascular lymphoid tissue, and elevated cytokines have been related to PAH pathogenesis but without a clear understanding of how these abnormalities are initiated, perpetuated, and connected in the progression of disease. We therefore set out to identify specific target antigens in PAH lung immune complexes as a starting point toward resolving these issues to better inform future application of immunomodulatory therapies.Lung immune complexes were isolated and PAH target antigens were identified by liquid chromatography tandem mass spectrometry, confirmed by enzyme-linked immunosorbent assay, and localized by confocal microscopy. One PAH antigen linked to immunity and inflammation was pursued and a link to PAH pathophysiology was investigated by next-generation sequencing, functional studies in cultured monocytes and endothelial cells, and hemodynamic and lung studies in a rat.SAM domain and HD domain-containing protein 1 (SAMHD1), an innate immune factor that suppresses HIV replication, was identified and confirmed as highly expressed in immune complexes from 16 hereditary and idiopathic PAH versus 12 control lungs. Elevated SAMHD1 was localized to endothelial cells, perivascular dendritic cells, and macrophages, and SAMHD1 antibodies were prevalent in tertiary lymphoid tissue. An unbiased screen using metagenomic sequencing related SAMHD1 to increased expression of human endogenous retrovirus K (HERV-K) in PAH versus control lungs (n=4). HERV-K envelope and deoxyuridine triphosphate nucleotidohydrolase mRNAs were elevated in PAH versus control lungs (n=10), and proteins were localized to macrophages. HERV-K deoxyuridine triphosphate nucleotidohydrolase induced SAMHD1 and proinflammatory cytokines (eg, interleukin 6, interleukin 1β, and tumor necrosis factor α) in circulating monocytes, pulmonary arterial endothelial cells, and also activated B cells. Vulnerability of pulmonary arterial endothelial cells (PAEC) to apoptosis was increased by HERV-K deoxyuridine triphosphate nucleotidohydrolase in an interleukin 6-independent manner. Furthermore, 3 weekly injections of HERV-K deoxyuridine triphosphate nucleotidohydrolase induced hemodynamic and vascular changes of pulmonary hypertension in rats (n=8) and elevated interleukin 6.Our study reveals that upregulation of the endogenous retrovirus HERV-K could both initiate and sustain activation of the immune system and cause vascular changes associated with PAH." @default.
- W2756682806 created "2017-10-06" @default.
- W2756682806 creator A5001067636 @default.
- W2756682806 creator A5002235585 @default.
- W2756682806 creator A5002732486 @default.
- W2756682806 creator A5009506633 @default.
- W2756682806 creator A5014721829 @default.
- W2756682806 creator A5016363572 @default.
- W2756682806 creator A5018766828 @default.
- W2756682806 creator A5031013450 @default.
- W2756682806 creator A5033995613 @default.
- W2756682806 creator A5035584392 @default.
- W2756682806 creator A5038851564 @default.
- W2756682806 creator A5040319012 @default.
- W2756682806 creator A5040495203 @default.
- W2756682806 creator A5044292612 @default.
- W2756682806 creator A5048865077 @default.
- W2756682806 creator A5049579219 @default.
- W2756682806 creator A5053909714 @default.
- W2756682806 creator A5058582407 @default.
- W2756682806 creator A5059331938 @default.
- W2756682806 creator A5061777081 @default.
- W2756682806 creator A5062175244 @default.
- W2756682806 creator A5066264659 @default.
- W2756682806 creator A5068801478 @default.
- W2756682806 creator A5071751288 @default.
- W2756682806 creator A5071972147 @default.
- W2756682806 creator A5074964358 @default.
- W2756682806 creator A5077984302 @default.
- W2756682806 creator A5081922859 @default.
- W2756682806 creator A5085893494 @default.
- W2756682806 date "2017-11-14" @default.
- W2756682806 modified "2023-10-06" @default.
- W2756682806 title "Upregulation of Human Endogenous Retrovirus-K Is Linked to Immunity and Inflammation in Pulmonary Arterial Hypertension" @default.
- W2756682806 cites W1967246550 @default.
- W2756682806 cites W1969951523 @default.
- W2756682806 cites W1976882578 @default.
- W2756682806 cites W1982971716 @default.
- W2756682806 cites W1983429163 @default.
- W2756682806 cites W1991684108 @default.
- W2756682806 cites W1997162550 @default.
- W2756682806 cites W1998346527 @default.
- W2756682806 cites W2000314052 @default.
- W2756682806 cites W2005377557 @default.
- W2756682806 cites W2013621351 @default.
- W2756682806 cites W2024407185 @default.
- W2756682806 cites W2024626836 @default.
- W2756682806 cites W2024859703 @default.
- W2756682806 cites W2027853473 @default.
- W2756682806 cites W2037199116 @default.
- W2756682806 cites W2046637170 @default.
- W2756682806 cites W2059744329 @default.
- W2756682806 cites W2068878293 @default.
- W2756682806 cites W2082084590 @default.
- W2756682806 cites W2082569794 @default.
- W2756682806 cites W2082918475 @default.
- W2756682806 cites W2104294858 @default.
- W2756682806 cites W2105461566 @default.
- W2756682806 cites W2108794690 @default.
- W2756682806 cites W2110051509 @default.
- W2756682806 cites W2111664429 @default.
- W2756682806 cites W2119656037 @default.
- W2756682806 cites W2124537265 @default.
- W2756682806 cites W2131047614 @default.
- W2756682806 cites W2132001965 @default.
- W2756682806 cites W2134228703 @default.
- W2756682806 cites W2137662380 @default.
- W2756682806 cites W2140482521 @default.
- W2756682806 cites W2140932173 @default.
- W2756682806 cites W2144724079 @default.
- W2756682806 cites W2145237733 @default.
- W2756682806 cites W2147296845 @default.
- W2756682806 cites W2149525857 @default.
- W2756682806 cites W2151942229 @default.
- W2756682806 cites W2157601642 @default.
- W2756682806 cites W2159335774 @default.
- W2756682806 cites W2163955468 @default.
- W2756682806 cites W2165494158 @default.
- W2756682806 cites W2207172864 @default.
- W2756682806 cites W2336019776 @default.
- W2756682806 cites W2533632435 @default.
- W2756682806 cites W2564191431 @default.
- W2756682806 cites W2587448772 @default.
- W2756682806 cites W2625184788 @default.
- W2756682806 doi "https://doi.org/10.1161/circulationaha.117.027589" @default.
- W2756682806 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5685911" @default.
- W2756682806 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28935667" @default.
- W2756682806 hasPublicationYear "2017" @default.
- W2756682806 type Work @default.
- W2756682806 sameAs 2756682806 @default.
- W2756682806 citedByCount "39" @default.
- W2756682806 countsByYear W27566828062017 @default.
- W2756682806 countsByYear W27566828062018 @default.
- W2756682806 countsByYear W27566828062019 @default.
- W2756682806 countsByYear W27566828062020 @default.
- W2756682806 countsByYear W27566828062021 @default.
- W2756682806 countsByYear W27566828062022 @default.
- W2756682806 countsByYear W27566828062023 @default.