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.

Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease / G. Corsetti, E. Pasini, T.M. Scarabelli, C. Romano, P.R. Agrawal, C. Chen-Scarabelli, R. Knight, L. Saravolatz, J. Narula, M. Ferrari-Vivaldi, V. Flati, D. Assanelli, F.S. Dioguardi. - In: JOURNAL OF GERIATRIC CARDIOLOGY. - ISSN 1671-5411. - 13:8(2016 Aug 28), pp. 701-711.

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

F.S. Dioguardi
2016-08-28

Abstract

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.
atherosclerotic disease; cardiomyocytes; cardiovascular risk; human heart; Klotho; geriatrics and gerontology; cardiology and cardiovascular medicine
Settore MED/09 - Medicina Interna
JOURNAL OF GERIATRIC CARDIOLOGY
Article (author)
File in questo prodotto:
File Dimensione Formato  
Dioguardi_DecreasedExpressionKlotho_2016.pdf

non disponibili

4.62 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/457022
Citazioni
  • ???jsp.display-item.citation.pmc??? 14
  • Scopus 25
  • ???jsp.display-item.citation.isi??? 25
social impact