Nuria Curbelo-Bermudez

Student NameNuria Curbelo-Bermudez
Faculty Mentor NameLeonardo Ferreira
CollegeCollege of Health and Human Performance
MajorApplied Physiology and Kinesiology
MinorDisabilities in Society
Research InterestsMuscle Physiology, Heart Failure,
Academic AwardsPresident’s Honor Role, Dean’s List, University Scholars Program 2020
OrganizationsU Matter, We Care Ambassador, College of Health and Human Performance Ambassador
Hobbies and InterestsPhotography, Volunteering, Fitness, Traveling, Nature

Research Project

Preventing Diaphragm Atrophy in Heart Failure with Reduced Ejection Fraction?

Heart failure with reduced ejection fraction (HFrEF) is an increasing epidemic that impacts millions of individuals worldwide. Each year there are half a million new cases reported in the United States alone. HFrEF is a prevalent and significant problem that affects multiple areas in the body such as breathing. This disorder leads to inspiratory implications such as difficulty or labored breathing (dyspnea), pulmonary congestion, and exercise intolerance. A primary source of these symptoms is diaphragm atrophy, a reduction in muscle fiber size. Diaphragm muscle weakness and atrophy are well documented in patients and animal models of HFrEF and, as the primary inspiratory muscle, diaphragm abnormalities contribute to inspiratory dysfunction. Although we know that heart failure leads to these life-threatening complications, the main causes are poorly understood.
Previous studies have shown that there are increased markers of reactive oxygen species (ROS) and oxidative stress in diaphragm samples from patients with HFrEF. High levels of ROS cause redox imbalance that can trigger diaphragm muscle atrophy leading to weakness. NADPH Oxidases (Nox) are a highly implicated source of the oxidative stress leading to atrophy, specifically the Nox2 isoform. Nox2 and its organizer subunit are heightened in the diaphragm of patients with HFrEF. I hypothesize that knocking out Nox2 will prevent excessive oxidative stress and diaphragm fiber atrophy in an animal model of HFrEF. To this end, I will investigate relative fiber type distribution and fiber cross sectional area of diaphragm muscle from an animal model in which Nox2 has been genetically knocked out from skeletal muscle. Furthermore, additional molecular mediators of atrophy will be tested for via western blot and real time PCR. This intervention aims to unveil mechanisms linking oxidative stress and diaphragm atrophy in HFrEF. Due to the high prevelence, morbidity, and mortality of HFrEF, there is a pressing need to comprehend underlying mechanisms leading to inspiratory dysfunction to improve patients’ overall quality of life and diminish morbidty and mortality.