Demonstrated the key role of a protein in cardiac hypertrophy

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ABC Health


Updated:05/14/2020 13: 12h


Researchers from the CIBER of Cardiovascular Diseases (CIBERCV) have analyzed the contribution of a protein (the NOR-1 nuclear receptor) to advancehypertensive cardiac hypertrophy, thanks to the creation of a transgenic mouse model. In this way, they open a new way to discover new therapies to cope with this disease, which is the main cause of heart failure, one of the most important health problems in our society.

“This study lays the foundations for new therapies that can prevent, stop or reverse the progression of this pathology”, indicates José Martínez González

As explained Cristina Rodríguez Sinovas“These animals have a greater predisposition to cardiac remodeling associated with aging and a greater susceptibility to developing cardiac hypertrophy induced by pressure overload, presenting a greater hypertrophy of the cardiomyocyte, more inflammation and fibrosis ».

Greater predisposition to accumulate collagen in the myocardium (fibrosis). – CIBER

This work, published in the journal Clinical Science, has been led by CIBERCV researchers José Martínez González, from the Barcelona Institute for Biomedical Research (IIBB-CSIC) and Cristina Rodríguez, from the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, in collaboration with Leif Hove-Madsen (IIBB-CSIC) and Juan Francisco Nistal (Hospital Universitario Marqués de Valdecilla de Santander), also researchers at the CIBERCV. In this study they have developed a transgenic mouse model that overexpresses NOR-1 human in the heart, demonstrating the relevant role in this disease.

These results indicate that this transgenic mouse can be useful as a new animal model in preclinical studies of molecules with therapeutic potential against cardiac hypertrophy. «The molecular mechanisms underlying this disease not fully understood, and the prevalence of heart failure is increasing worldwide, while effective treatments remain elusive.

Therefore, the generation of these models that will allow the development of new therapies to attack the pathological remodeling of the heart with the intention of preventing, stopping or reversing the progression of this disease “, indicates the group leader of the CIBERCVJosé Martínez González.

Greater remodeling associated with aging detected in the left ventricle of transgenic animals

The developed transgenic mice have overexpressed NOR-1 in the heart, mainly in cardiomyocytes, who experienced an increase in cell size, but also in cardiofibroblasts (more likely to synthesize collagen and migrate); and they have also developed a greater remodeling associated with the aging of the left ventricle.

Jose Martinez and Cristina Rodriguez, CIBERCV-CSIC-St Pau researchers.
Jose Martinez and Cristina Rodriguez, CIBERCV-CSIC-St Pau researchers. – CIBER

“We determine that the receptor NOR-1 positively regulates two key genes involved in cardiac hypertrophy and fibrosis.Therefore, our findings suggest that this receptor is involved in the transcriptional program that leads to hypertensive cardiac hypertrophy», Indicates Dr. Martínez González.

One of the main public health problems in the world

Hypertensive cardiac hypertrophy (HCH) is an answer compensatory of the heart to neurohormonal stress and overload hemodynamics (eg, derived from hypertension and valvular diseases) whose prolongation in time leads to congestive heart failure (HF), the main cause of hospitalization in the elderly and one of the public health problems worldwide.

According to recent studies, the prevalence of this disease doubles with each decade of age and is around 10% in those over 70. Control of risk factors, such as hypertension and ischemic heart disease, in addition to unhealthy lifestyle habitsThey are the only way to control the foreseeable increase in this disease in the future.



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