A5010833642- Autophagy in Disease and Therapy
- Cardiac Ischemia and Reperfusion
- Mitochondrial Function and Pathology
- Signaling Pathways in Disease
- Endoplasmic Reticulum Stress and Disease
- Genetic and Kidney Cyst Diseases
- ATP Synthase and ATPases Research
- Histone Deacetylase Inhibitors Research
- Microtubule and mitosis dynamics
- Cardiovascular Function and Risk Factors
- Cardiac Arrest and Resuscitation
- Cardiomyopathy and Myosin Studies
- Cardiac Fibrosis and Remodeling
- Sirtuins and Resveratrol in Medicine
- Nitric Oxide and Endothelin Effects
- Peptidase Inhibition and Analysis
- Cellular transport and secretion
- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Nicotinic Acetylcholine Receptors Study
- Connective Tissue Growth Factor Research
- Cellular Mechanics and Interactions
- Cardiovascular Disease and Adiposity
- Cardiac, Anesthesia and Surgical Outcomes
- Cardiac Structural Anomalies and Repair
University of Chile
2015-2024
Advanced Center for Chronic Diseases
2014-2023
Fundación Chile
2021
Pontificia Universidad Católica de Chile
2021
Instituto de Neurociencia Biomédica
2019
The University of Texas Southwestern Medical Center
2013-2018
Southwestern Medical Center
2013-2015
Yale University
2015
Instituto de Ciências Farmacêuticas
2011
Centro de Estudios Científicos
2010
Reperfusion accounts for a substantial fraction of the myocardial injury occurring with ischemic heart disease. Yet, no standard therapies are available targeting reperfusion injury. Here, we tested hypothesis that suberoylanilide hydroxamic acid (SAHA), histone deacetylase inhibitor approved cancer treatment by US Food and Drug Administration, will blunt injury.Twenty-one rabbits were randomly assigned to 3 groups: (1) vehicle control, (2) SAHA pretreatment (1 day before at surgery), (3)...
Mitochondria are key organelles for ATP production in cardiomyocytes, which is regulated by processes of fission and fusion. We hypothesized that the mitochondria fusion protein dynamin-related 1 (Drp1) inhibition, attenuates ischemia-reperfusion (I/R) injury through modifications mitochondrial metabolism. Rats were subjected to I/R coronary artery ligation, isolated cardiomyocytes treated with an ischemia-mimicking solution. In vivo, cardiac function, myocardial infarction area, morphology...
Our objective was to investigate in cardiac muscle the contribution of NADPH oxidase (a) ryanodine receptor-2 (RyR2) S-glutathionylation and (b) preconditioning effects exercise tachycardia on infarct size following coronary artery occlusion.We measured activity, RyR2 S-glutathionylation, calcium release kinetics sarcoplasmic reticulum (SR) vesicles isolated from dog ventricular after tachycardia, plus or minus prior administration inhibitor apocynin. In sections, we studied colocalization...
Altering chromatin structure through histone posttranslational modifications has emerged as a key driver of transcriptional responses in cells. Modulation these by pharmacological inhibition class I deacetylases (HDACs), group remodeling enzymes, been successful blocking the growth some cancer cell types. These inhibitors also attenuate pathogenesis pathological cardiac blunting and even reversing hypertrophy. The mechanistic target rapamycin (mTOR) is critical sensor regulator that, part...
Background— L-type calcium channel activity is critical to afterload-induced hypertrophic growth of the heart. However, mechanisms governing mechanical stress–induced activation are obscure. Polycystin-1 (PC-1) a G protein–coupled receptor–like protein that functions as mechanosensor in variety cell types and present cardiomyocytes. Methods Results— We subjected neonatal rat ventricular myocytes stretch by exposing them hypo-osmotic medium or cyclic stretch, triggering manner dependent on...
The regulator of calcineurin 1 (RCAN1) inhibits CN (calcineurin), a Ca2+-activated protein phosphatase important in cardiac remodeling. In humans, RCAN1 is located on chromosome 21 proximity to the Down syndrome critical region. hearts and brains Rcan1 KO mice are more susceptible damage from ischemia/reperfusion (I/R); however, underlying cause not known.Mitochondria key mediators I/R damage. goal these studies was determine impact mitochondrial dynamics function.Using both neonatal...
Chaperone-mediated autophagy (CMA) is a selective mechanism for the degradation of soluble cytosolic proteins bearing sequence KFERQ. These are targeted by chaperones and delivered to lysosomes where they translocated into lysosomal lumen degraded via lysosome-associated membrane protein type 2A (LAMP-2A). Mutations in LAMP2 that inhibit result Danon disease characterized hypertrophic cardiomyopathy. The ryanodine receptor 2 (RyR2) plays key role cardiomyocyte excitation-contraction its...
Ventricular arrhythmias are a common cause of sudden cardiac death, and their occurrence is higher in obese subjects. Abnormal gating ryanodine receptors (RyR2), the calcium release channels sarcoplasmic reticulum, can produce ventricular arrhythmias. Since obesity promotes oxidative stress RyR2 redox-sensitive channels, we investigated whether activity was altered mice. Mice fed high fat diet (HFD) became after eight weeks exhibited significant increase Single isolated from hearts mice were...