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Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease

BACKGROUND: Klotho proteins (α- and β) are membrane-based circulating proteins that regulate cell metabolism, as well as the lifespan modulating activity of Fibroblast Growth Factors (FGFs). Recent data has shown that higher plasma circulating Klotho levels reduce cardiovascular risk, suggesting Klo...

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Autores principales: Corsetti, Giovanni, Pasini, Evasio, Scarabelli, Tiziano M, Romano, Claudia, Agrawal, Pratik R, Chen-Scarabelli, Carol, Knight, Richard, Saravolatz, Louis, Narula, Jagat, Ferrari-Vivaldi, Mario, Flati, Vincenzo, Assanelli, Deodato, Dioguardi, Francesco S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Science Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067432/
https://www.ncbi.nlm.nih.gov/pubmed/27781061
http://dx.doi.org/10.11909/j.issn.1671-5411.2016.08.009
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author Corsetti, Giovanni
Pasini, Evasio
Scarabelli, Tiziano M
Romano, Claudia
Agrawal, Pratik R
Chen-Scarabelli, Carol
Knight, Richard
Saravolatz, Louis
Narula, Jagat
Ferrari-Vivaldi, Mario
Flati, Vincenzo
Assanelli, Deodato
Dioguardi, Francesco S
author_facet Corsetti, Giovanni
Pasini, Evasio
Scarabelli, Tiziano M
Romano, Claudia
Agrawal, Pratik R
Chen-Scarabelli, Carol
Knight, Richard
Saravolatz, Louis
Narula, Jagat
Ferrari-Vivaldi, Mario
Flati, Vincenzo
Assanelli, Deodato
Dioguardi, Francesco S
author_sort Corsetti, Giovanni
collection PubMed
description BACKGROUND: Klotho proteins (α- and β) are membrane-based circulating proteins that regulate cell metabolism, as well as the lifespan modulating activity of Fibroblast Growth Factors (FGFs). Recent data has shown that higher plasma circulating Klotho levels reduce cardiovascular risk, suggesting Klotho has a protective role in cardiovascular diseases. However, although so far it has been identified in various organs, it is unknown whether cardiomyocytes express Klotho and FGFs, and whether high cardiovascular risk could affect cardiac expression of Klotho, FGFs and other molecules. METHODS: We selected 20 patients with an estimated 10-year high atherosclerotic cardiovascular disease and 10 age-matched control subjects with an estimated 10-year low risk undergone cardiac surgery for reasons other than coronary artery by-pass. In myocardial biopsies, we evaluated by immuno-histochemistry whether Klotho and FGFs were expressed in cardiomyocytes, and whether higher cardiovascular risk influenced the expression of other molecules involved in endoplasmic reticulum stress, oxidative stress, inflammation and fibrosis. RESULTS: Only cardiomyocytes of patients with a higher cardiovascular risk showed lower expression of Klotho, but higher expressions of FGFs. Furthermore, higher cardiovascular risk was associated with increased expression of oxidative and endoplasmic reticular stress, inflammation and fibrosis. CONCLUSIONS: This study showed for the first time that Klotho proteins are expressed in human cardiomyocytes and that cardiac expression of Klotho is down-regulated in higher cardiovascular risk patients, while expression of stress-related molecules were significantly increased.
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spelling pubmed-50674322016-10-25 Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease Corsetti, Giovanni Pasini, Evasio Scarabelli, Tiziano M Romano, Claudia Agrawal, Pratik R Chen-Scarabelli, Carol Knight, Richard Saravolatz, Louis Narula, Jagat Ferrari-Vivaldi, Mario Flati, Vincenzo Assanelli, Deodato Dioguardi, Francesco S J Geriatr Cardiol Research Article BACKGROUND: Klotho proteins (α- and β) are membrane-based circulating proteins that regulate cell metabolism, as well as the lifespan modulating activity of Fibroblast Growth Factors (FGFs). Recent data has shown that higher plasma circulating Klotho levels reduce cardiovascular risk, suggesting Klotho has a protective role in cardiovascular diseases. However, although so far it has been identified in various organs, it is unknown whether cardiomyocytes express Klotho and FGFs, and whether high cardiovascular risk could affect cardiac expression of Klotho, FGFs and other molecules. METHODS: We selected 20 patients with an estimated 10-year high atherosclerotic cardiovascular disease and 10 age-matched control subjects with an estimated 10-year low risk undergone cardiac surgery for reasons other than coronary artery by-pass. In myocardial biopsies, we evaluated by immuno-histochemistry whether Klotho and FGFs were expressed in cardiomyocytes, and whether higher cardiovascular risk influenced the expression of other molecules involved in endoplasmic reticulum stress, oxidative stress, inflammation and fibrosis. RESULTS: Only cardiomyocytes of patients with a higher cardiovascular risk showed lower expression of Klotho, but higher expressions of FGFs. Furthermore, higher cardiovascular risk was associated with increased expression of oxidative and endoplasmic reticular stress, inflammation and fibrosis. CONCLUSIONS: This study showed for the first time that Klotho proteins are expressed in human cardiomyocytes and that cardiac expression of Klotho is down-regulated in higher cardiovascular risk patients, while expression of stress-related molecules were significantly increased. Science Press 2016-08 /pmc/articles/PMC5067432/ /pubmed/27781061 http://dx.doi.org/10.11909/j.issn.1671-5411.2016.08.009 Text en Institute of Geriatric Cardiology http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission.
spellingShingle Research Article
Corsetti, Giovanni
Pasini, Evasio
Scarabelli, Tiziano M
Romano, Claudia
Agrawal, Pratik R
Chen-Scarabelli, Carol
Knight, Richard
Saravolatz, Louis
Narula, Jagat
Ferrari-Vivaldi, Mario
Flati, Vincenzo
Assanelli, Deodato
Dioguardi, Francesco S
Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease
title Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease
title_full Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease
title_fullStr Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease
title_full_unstemmed Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease
title_short Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease
title_sort decreased expression of klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067432/
https://www.ncbi.nlm.nih.gov/pubmed/27781061
http://dx.doi.org/10.11909/j.issn.1671-5411.2016.08.009
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