title: Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease.
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.
authors: Department of Clinical & Experimental Sciences, Division of Human Anatomy & Physiopathology, University of Brescia, Brescia, Italy.
authors: Giovanni
authors: G
authors: Corsetti
authors: "S.Maugeri Foundation", IRCCS, Cardiology Division, Medical Centre of Lumezzane, Brescia, Italy.
authors: Evasio
authors: E
authors: Pasini
authors: Zena and Michael A, Wiener Cardiovascular Institute, Mount Sinai Medical Center, New York, USA; Center for Heart and Vessel Preclinical Studies, St. John Hospital & Medical Center, Wayne State University School of Medicine, Detroit, USA.
authors: Tiziano M
authors: TM
authors: Scarabelli
authors: Department of Clinical & Experimental Sciences, Division of Human Anatomy & Physiopathology, University of Brescia, Brescia, Italy.
authors: Claudia
authors: C
authors: Romano
authors: Zena and Michael A, Wiener Cardiovascular Institute, Mount Sinai Medical Center, New York, USA.
authors: Pratik R
authors: PR
authors: Agrawal
authors: VA Ann Arbor Health Care System, University of Michigan, Ann Arbor, USA.
authors: Carol
authors: C
authors: Chen-Scarabelli
authors: Center for Heart and Vessel Preclinical Studies, St. John Hospital & Medical Center, Wayne State University School of Medicine, Detroit, USA.
authors: Richard
authors: R
authors: Knight
authors: Center for Heart and Vessel Preclinical Studies, St. John Hospital & Medical Center, Wayne State University School of Medicine, Detroit, USA.
authors: Louis
authors: L
authors: Saravolatz
authors: Zena and Michael A, Wiener Cardiovascular Institute, Mount Sinai Medical Center, New York, USA.
authors: Jagat
authors: J
authors: Narula
authors: Department of Cardiovascular Surgery, "San Rocco" Hospital, Ome, Brescia, Italy.
authors: Mario
authors: M
authors: Ferrari-Vivaldi
authors: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
authors: Vincenzo
authors: V
authors: Flati
authors: Division of Sport-Internal Medicine, Department of Clinical & Experimental Sciences, University of Brescia, Brescia, Italy.
authors: Deodato
authors: D
authors: Assanelli
authors: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors: Francesco S
authors: FS
authors: Dioguardi
keywords: Atherosclerotic disease; Cardiomyocytes; Cardiovascular risk; Human heart; Klotho