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Authordc.contributor.authorOcaranza, María Paz 
Authordc.contributor.authorValderas, Patricio 
Authordc.contributor.authorMoya, Jackeline 
Authordc.contributor.authorGabrielli, Luigi 
Authordc.contributor.authorGodoy, Iván 
Authordc.contributor.authorCórdava, Samuel 
Authordc.contributor.authorMac Nab, Paul 
Authordc.contributor.authorGarcía Nannig, Lorena 
Authordc.contributor.authorFarías, Luis 
Authordc.contributor.authorJalil, Jorge E. 
Admission datedc.date.accessioned2020-06-11T22:13:13Z
Available datedc.date.available2020-06-11T22:13:13Z
Publication datedc.date.issued2020
Cita de ítemdc.identifier.citationCardiovasc Diabetol (2020) 19:56es_ES
Identifierdc.identifier.other10.1186/s12933-020-01027-2
Identifierdc.identifier.urihttp://repositorio.uchile.cl/handle/2250/175412
Abstractdc.description.abstractBackgroundThe intracellular ROCK signaling pathway is an important modulator of blood pressure and of cardiovascular and renal remodeling when Rho-kinase activity is increased. Besides, in preclinical models of diabetes, ROCK activation has also a role in abnormal glucose metabolism as well as in subsequent vascular and myocardial dysfunction. In humans, there are a few data assessing ROCK activation in patients with type 2 diabetes mellitus (T2D) and no studies assessing upstream/downstream components of the ROCK pathway. We assessed here levels of ROCK activation and some of the RhoA/ROCK cascade molecules in peripheral blood mononuclear cells (PBMCs) in T2D patients under current treatment.MethodsCross-sectional observational study comparing 28 T2D patients under current antidiabetic treatment with 31 consecutive healthy subjects, matched by age and gender. Circulating levels of malondialdehyde, angiotensin II and inflammatory cytokines IL-6 and IL-8 were determined in all subjects. ROCK activation in PMBCs, upstream and downstream cascade proteins, and levels of the proinflammatory molecules VCAM, ICAM-1 and IL-8 were determined in their PMBCs by Western blot.ResultsCompared to healthy controls, ROCK activation in T2D patients measured by 2 direct ROCK targets in PBMCs was increased by 420 and 570% (p<0001) and it correlated significantly with serum glucose levels. p38 MAPK phosphorylation (downstream from ROCK) and JAK-2 (upstream from ROCK) were significantly higher in the T2D patients by 580% and 220%, respectively. In T2D patients, significantly increased PBMC levels of the proinflammatory molecules VCAM-1, ICAM-1 and IL-8 were observed compared to control subjects (by 180%, 360% and 260%, respectively). Circulating levels of Ang II and MDA were significantly higher in T2D patients by 29 and 63%, respectively.ConclusionsT2D patients under treatment with glucose-lowering drugs, antihypertensive treatment as well as with statins have significantly increased ROCK activation in their circulating leukocytes along with higher phosphorylation of downstream cascade proteins despite pharmacologic treatment, along with increased plasma angiotensin II and MDA levels. ROCK inhibition might have an additional role in the prevention and treatment of T2D.es_ES
Patrocinadordc.description.sponsorshipAgencia Nacional de Investigacion y Desarrollo (ANID, Chile): Fondecyt (Fondo Nacional de Desarrollo Cientiico y Tecnologico, Chile) 1161739 1121060 FONDAP 15130011 Anillo ACT192144es_ES
Lenguagedc.language.isoenes_ES
Publisherdc.publisherBMCes_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile*
Link to Licensedc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/*
Sourcedc.sourceCardiovascular Diabetologyes_ES
Keywordsdc.subjectDiabeteses_ES
Keywordsdc.subjectMetabolic syndromees_ES
Keywordsdc.subjectRho kinasees_ES
Keywordsdc.subjectROCKes_ES
Keywordsdc.subjectMYPT-1es_ES
Keywordsdc.subjectERMes_ES
Keywordsdc.subjectFasudiles_ES
Keywordsdc.subjectJAKes_ES
Keywordsdc.subjectp38 MAPKes_ES
Keywordsdc.subjectMetformines_ES
Títulodc.titleRho kinase cascade activation in circulating leukocytes in patients with diabetes mellitus type 2es_ES
Document typedc.typeArtículo de revistaes_ES
Catalogueruchile.catalogadorapces_ES
Indexationuchile.indexArtículo de publicación ISIes_ES


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Attribution-NonCommercial-NoDerivs 3.0 Chile
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Chile