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Clinical and Proteomic Correlates of Plasma ACE2 (Angiotensin-Converting Enzyme 2) in Human Heart Failure.
Chirinos, Julio A; Cohen, Jordana B; Zhao, Lei; Hanff, Thomas; Sweitzer, Nancy; Fang, James; Corrales-Medina, Vicente; Anmar, Ron; Morley, Michael; Zamani, Payman; Bhattacharya, Priyanka; Brandimarto, Jeff; Jia, Yi; Basso, Michael D; Wang, Zhaoqing; Ebert, Christina; Ramirez-Valle, Francisco; Schafer, Peter H; Seiffert, Dietmar; Gordon, David A; Cappola, Thomas.
  • Chirinos JA; From the Hospital of the University of Pennsylvania, Philadelphia (J.A.C., J.B.C., T.H., M.M., P.Z., P.B., J.B., T.C.).
  • Cohen JB; University of Pennsylvania Perelman School of Medicine, Philadelphia (J.A.C., J.B.C., T.H., M.M., P.Z., P.B., J.B., T.C.).
  • Zhao L; From the Hospital of the University of Pennsylvania, Philadelphia (J.A.C., J.B.C., T.H., M.M., P.Z., P.B., J.B., T.C.).
  • Hanff T; University of Pennsylvania Perelman School of Medicine, Philadelphia (J.A.C., J.B.C., T.H., M.M., P.Z., P.B., J.B., T.C.).
  • Sweitzer N; Bristol Myers Squibb Company, Princeton, NJ (L.Z., R.A., M.D.B., Z.W., C.E., F.R.-V., P.H.S., D.S., D.A.G.).
  • Fang J; From the Hospital of the University of Pennsylvania, Philadelphia (J.A.C., J.B.C., T.H., M.M., P.Z., P.B., J.B., T.C.).
  • Corrales-Medina V; University of Pennsylvania Perelman School of Medicine, Philadelphia (J.A.C., J.B.C., T.H., M.M., P.Z., P.B., J.B., T.C.).
  • Anmar R; Sarver Heart Institute, University of Arizona, Tuscon (N.S.).
  • Morley M; University of Utah, Salt Lake City (J.F.).
  • Zamani P; The Ottawa Hospital Research Institute and University of Ottawa, Ontario, Canada (V.C.M.).
  • Bhattacharya P; Bristol Myers Squibb Company, Princeton, NJ (L.Z., R.A., M.D.B., Z.W., C.E., F.R.-V., P.H.S., D.S., D.A.G.).
  • Brandimarto J; From the Hospital of the University of Pennsylvania, Philadelphia (J.A.C., J.B.C., T.H., M.M., P.Z., P.B., J.B., T.C.).
  • Jia Y; University of Pennsylvania Perelman School of Medicine, Philadelphia (J.A.C., J.B.C., T.H., M.M., P.Z., P.B., J.B., T.C.).
  • Basso MD; From the Hospital of the University of Pennsylvania, Philadelphia (J.A.C., J.B.C., T.H., M.M., P.Z., P.B., J.B., T.C.).
  • Wang Z; University of Pennsylvania Perelman School of Medicine, Philadelphia (J.A.C., J.B.C., T.H., M.M., P.Z., P.B., J.B., T.C.).
  • Ebert C; From the Hospital of the University of Pennsylvania, Philadelphia (J.A.C., J.B.C., T.H., M.M., P.Z., P.B., J.B., T.C.).
  • Ramirez-Valle F; University of Pennsylvania Perelman School of Medicine, Philadelphia (J.A.C., J.B.C., T.H., M.M., P.Z., P.B., J.B., T.C.).
  • Schafer PH; From the Hospital of the University of Pennsylvania, Philadelphia (J.A.C., J.B.C., T.H., M.M., P.Z., P.B., J.B., T.C.).
  • Seiffert D; University of Pennsylvania Perelman School of Medicine, Philadelphia (J.A.C., J.B.C., T.H., M.M., P.Z., P.B., J.B., T.C.).
  • Gordon DA; SomaLogic Inc, Boulder, CO (Y.J.).
  • Cappola T; From the Hospital of the University of Pennsylvania, Philadelphia (J.A.C., J.B.C., T.H., M.M., P.Z., P.B., J.B., T.C.).
Hypertension ; 76(5): 1526-1536, 2020 11.
Статья в английский | MEDLINE | ID: covidwho-2153220
ABSTRACT
ACE2 (angiotensin-converting enzyme 2) is a key component of the renin-angiotensin-aldosterone system. Yet, little is known about the clinical and biologic correlates of circulating ACE2 levels in humans. We assessed the clinical and proteomic correlates of plasma (soluble) ACE2 protein levels in human heart failure. We measured plasma ACE2 using a modified aptamer assay among PHFS (Penn Heart Failure Study) participants (n=2248). We performed an association study of ACE2 against ≈5000 other plasma proteins measured with the SomaScan platform. Plasma ACE2 was not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 was associated with older age, male sex, diabetes mellitus, a lower estimated glomerular filtration rate, worse New York Heart Association class, a history of coronary artery bypass surgery, and higher pro-BNP (pro-B-type natriuretic peptide) levels. Plasma ACE2 exhibited associations with 1011 other plasma proteins. In pathway overrepresentation analyses, top canonical pathways associated with plasma ACE2 included clathrin-mediated endocytosis signaling, actin cytoskeleton signaling, mechanisms of viral exit from host cells, EIF2 (eukaryotic initiation factor 2) signaling, and the protein ubiquitination pathway. In conclusion, in humans with heart failure, plasma ACE2 is associated with various clinical factors known to be associated with severe coronavirus disease 2019 (COVID-19), including older age, male sex, and diabetes mellitus, but is not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 protein levels are prominently associated with multiple cellular pathways involved in cellular endocytosis, exocytosis, and intracellular protein trafficking. Whether these have a causal relationship with ACE2 or are relevant to novel coronavirus-2 infection remains to be assessed in future studies.
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Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Основная тема: Pneumonia, Viral / Disease Outbreaks / Coronavirus Infections / Peptidyl-Dipeptidase A / Disease Progression / Heart Failure Тип исследования: Когортное исследование / Диагностическое исследование / Наблюдательное исследование / Прогностическое исследование Пределы темы: Женщины / Люди / Мужчины / Middle aged Страна как тема: Северная Америка Язык: английский Журнал: Hypertension Год: 2020 Тип: Статья

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Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Основная тема: Pneumonia, Viral / Disease Outbreaks / Coronavirus Infections / Peptidyl-Dipeptidase A / Disease Progression / Heart Failure Тип исследования: Когортное исследование / Диагностическое исследование / Наблюдательное исследование / Прогностическое исследование Пределы темы: Женщины / Люди / Мужчины / Middle aged Страна как тема: Северная Америка Язык: английский Журнал: Hypertension Год: 2020 Тип: Статья