ArticleHeart and vessels2017
Conditional knockout of activin like kinase-1 (ALK-1) leads to heart failure without maladaptive remodeling.
Article in Heart and vessels, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Coordinated expression of BMP10/ALK1/endoglin-proteins that drive embryonic cardiac and vascular morphogenesis-in patients with heart failure: The EMPEROR Program.European journal of heart failure · 2025Article
- Updates on the Pathogenesis and Therapeutic Approaches for Hereditary Hemorrhagic Telangiectasia.Current vascular pharmacology · 2025Review
- ALK1 Signaling in Human Cardiac Progenitor Cells Promotes a Pro-angiogenic Secretome.Journal of cellular signaling · 2024Article
- Loss of Bone Morphogenetic Protein-9 Reduces Survival and Increases MMP Activity After Myocardial Infarction.JACC. Basic to translational science · 2023Article
- Deficiency in hereditary hemorrhagic telangiectasia-associated Endoglin elicits hypoxia-driven heart failure in zebrafish.Disease models & mechanisms · 2023Article
- Different cardiovascular and pulmonary phenotypes for single- and double-knock-out mice deficient in BMP9 and BMP10.Cardiovascular research · 2022Article
- Endothelial Activin Receptor-Like Kinase 1 (ALK1) Regulates Myofibroblast Emergence and Peritubular Capillary Stability in the Early Stages of Kidney Fibrosis.Frontiers in pharmacology · 2022Article
- Metformin suppresses proliferation and differentiation induced by BMP9Frontiers in pharmacology · 2022Article
- Cerebrovascular and cardiovascular disease burden in patients with hereditary hemorrhagic telangiectasia.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Observational
- Exogenous BMP9 promotes lung fibroblast HFL-1 cell activation via ALK1/Smad1/5 signalingExperimental and therapeutic medicine · 2021Article
- Subaortic Membranes in Patients With Hereditary Hemorrhagic Telangiectasia and Liver Vascular Malformations.Journal of the American Heart Association · 2020Observational
- Alk1 haploinsufficiency causes glomerular dysfunction and microalbuminuria in diabetic mice.Scientific reports · 2020Article
- BMP10-mediated ALK1 signaling is continuously required for vascular development and maintenance.Angiogenesis · 2020Article
- Loss of Endothelial Endoglin Promotes High-Output Heart Failure Through Peripheral Arteriovenous Shunting Driven by VEGF Signaling.Circulation research · 2020Article
- Abdominal Positioning of the Next-Generation Intra-Aortic Fluid Entrainment Pump (Aortix) Improves Cardiac Output in a Swine Model of Heart Failure.Circulation. Heart failure · 2018Article
- Interventions and mechanisms of N-acetylcysteine on monocrotaline-induced pulmonary arterial hypertension.Experimental and therapeutic medicine · 2018Article
- ALK1 signaling in development and disease: new paradigms.Cellular and molecular life sciences : CMLS · 2017Review
- High soluble endoglin levels do not induce changes in structural parameters of mouse heart.Heart and vessels · 2017Article
- Reduced activin receptor-like kinase 1 activity promotes cardiac fibrosis in heart failure.Cardiovascular pathology : the official journal of the Society for Cardiovascular PathologyArticle
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Activin like kinase-1 (AlK-1) mediates signaling via the transforming growth factor beta (TGFβ) family of ligands. AlK-1 activity promotes endothelial proliferation and migration. Reduced AlK-1 activity is associated with arteriovenous malformations. No studies have examined the effect of global AlK-1 deletion on indices of cardiac remodeling. We hypothesized that reduced levels of AlK-1 promote maladaptive cardiac remodeling. To test this hypothesis, we employed AlK-1 conditional knockout mice (cKO) harboring the ROSA26-CreER knock-in allele, whereby a single dose of intraperitoneal tamoxifen triggered ubiquitous Cre recombinase-mediated excision of floxed AlK-1 alleles. Tamoxifen treated wild-type (WT-TAM; n = 5) and vehicle treated AlK-1-cKO mice (cKO-CON; n = 5) served as controls for tamoxifen treated AlK-1-cKO mice (cKO-TAM; n = 15). AlK-1 cKO-TAM mice demonstrated reduced 14-day survival compared to cKO-CON controls (13 vs 100%, respectively, p < 0.01). Seven days after treatment, cKO-TAM mice exhibited reduced left ventricular (LV) fractional shortening, progressive LV dilation, and gastrointestinal bleeding. After 14 days total body mass was reduced, but LV and lung mass increased in cKO-TAM not cKO-CON mice. Peak LV systolic pressure, contractility, and arterial elastance were reduced, but LV end-diastolic pressure and stroke volume were increased in cKO-TAM, not cKO-CON mice. LV AlK-1 mRNA levels were reduced in cKO-TAM, not cKO-CON mice. LV levels of other TGFβ-family ligands and receptors (AlK5, TBRII, BMPRII, Endoglin, BMP7, BMP9, and TGFβ1) were unchanged between groups. Cardiomyocyte area and LV levels of BNP were increased in cKO-TAM mice, but LV levels of β-MHC and SERCA were unchanged. No increase in markers of cardiac fibrosis, Type I collagen, CTGF, or PAI-1, were observed between groups. No differences were observed for any variable studied between cKO-CON and WT-TAM mice. Global deletion of AlK-1 is associated with the development of high output heart failure without maladaptive remodeling. Future studies exploring the functional role of AlK-1 in cardiac remodeling independent of systemic AVMs are required.
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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.