ArticleJournal of molecular medicine (Berlin, Germany)2011
Inactivation of endothelial proprotein convertase 5/6 decreases collagen deposition in the cardiovascular system: role of fibroblast autophagy.
Article in Journal of molecular medicine (Berlin, Germany), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Genetic and clinical determinants of abdominal aortic diameter: genome-wide association studies, exome array data and Mendelian randomization study.Human molecular genetics · 2022Pooled it
- PCSK5 promotes angiogenesis and cardiac repair after myocardial infarction.Nature communications · 2026Article
- Single-Nuclei RNA-Sequencing of the Gastrocnemius Muscle in Peripheral Artery Disease.Circulation research · 2023Article
- Apoptotic exosome-like vesicles transfer specific and functional mRNAs to endothelial cells by phosphatidylserine-dependent macropinocytosis.Cell death & disease · 2023Article
- Urine peptidome analysis in cardiorenal syndrome reflects molecular processes.Scientific reports · 2021Article
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- Proprotein convertase inhibition: Paralyzing the cell's master switches.Biochemical pharmacology · 2017Review
- Thrombin activation of protein C requires prior processing by a liver proprotein convertase.The Journal of biological chemistry · 2017Article
- Formation of mitochondrial-derived vesicles is an active and physiologically relevant mitochondrial quality control process in the cardiac system.The Journal of physiology · 2016Article
- Posttranslational processing of FGF23 in osteocytes during the osteoblast to osteocyte transition.Bone · 2016Article
- Estrogen stimuli promote osteoblastic differentiation via the subtilisin-like proprotein convertase PACE4 in MC3T3-E1 cells.Journal of bone and mineral metabolism · 2015Article
- Circulating collagen biomarkers as indicators of disease severity in pulmonary arterial hypertension.JACC. Heart failure · 2014Observational
- Furin is the primary in vivo convertase of angiopoietin-like 3 and endothelial lipase in hepatocytes.The Journal of biological chemistry · 2013Article
- Loss of endothelial furin leads to cardiac malformation and early postnatal death.Molecular and cellular biology · 2012Article
- The biology and therapeutic targeting of the proprotein convertases.Nature reviews. Drug discovery · 2012Review
- Time for endothelial cell proprotein convertase PC5/6 in cardiovascular medicine?Journal of molecular medicine (Berlin, Germany) · 2011Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Proprotein convertase (PC) 5/6 belongs to a family of secretory proteases involved in proprotein proteolysis. Several studies suggest a role for PC5/6 in cardiovascular disease. Because lethality at birth of mice lacking PC5/6 precluded elucidation of its function in the adult, we generated mice in which the gene of PC5/6 (pcsk5) is specifically inactivated in endothelial cells (ecKO), which are viable and do not exhibit overt abnormalities. In order to uncover the function of PC5/6 in the cardiovascular system, the effect of ecKO was studied in aging mice. In 16 to 18-month-old ecKO mice, the left ventricle (LV) mass, media cross-sectional area of aorta and coronary arteries, and media-to-lumen ratio of mesenteric arteries were decreased. The LV presented decreased diastolic function, and mesenteric arteries showed decreased stiffness. Collagen was decreased in the LV myocardial interstitium and perivascularly in coronary arteries and aorta. Cardiovascular hypotrophy likely develops with aging, since no significant changes were observed in 2-month-old ecKO mice. Fibroblasts, as a source of collagen in myocardium and vasculature, may play a role in the decrease in collagen deposition. Fibroblasts co-cultured with ecKO endothelial cells showed decreased collagen production, decreased insulin-like growth factor (IGF)-1/Akt/mTOR signaling, and enhanced autophagic activation. PC5/6 inactivation in endothelial cells results in cardiovascular hypotrophy associated with decreased collagen deposition, decreased LV diastolic function, and vascular stiffness, suggesting a trophic role of endothelial PC5/6 in the cardiovascular system, likely mediated by IGF-1/Akt/mTOR signaling and control of autophagy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.