Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Dec 12:12:350.
doi: 10.1186/s12967-014-0350-7.

Uncovering the cathepsin system in heart failure patients submitted to Left Ventricular Assist Device (LVAD) implantation

Andrea D'Amico  1 , Rosetta Ragusa  2 , Raffaele Caruso  3 , Tommaso Prescimone  4 , Sandra Nonini  5 , Manuela Cabiati  6 , Silvia Del Ry  7 , Maria Giovanna Trivella  8 , Daniela Giannessi  9 , Chiara Caselli  10
Affiliations

Uncovering the cathepsin system in heart failure patients submitted to Left Ventricular Assist Device (LVAD) implantation

Andrea D'Amico et al. J Transl Med. .

Abstract

Background: In end-stage heart failure (HF), the implantation of a left ventricular assist device (LVAD) is able to induce reverse remodeling. Cellular proteases, such as cathepsins, are involved in the progression of HF. The aim of this study was to evaluate the role of cathepsin system in HF patients supported by LVAD, in order to determine their involvement in cardiac remodeling.

Methods: The expression of cysteine (CatB, CatK, CatL, CatS) and serine cathepsin (CatG), and relative inhibitors (Cystatin B, C and SerpinA3, respectively) was determined in cardiac biopsies of 22 patients submitted to LVAD (pre-LVAD) and compared with: 1) control stable chronic HF patients on medical therapy at the moment of heart transplantation without prior LVAD (HT, n = 7); 2) patients supported by LVAD at the moment of transplantation (post-LVAD, n = 6).

Results: The expression of cathepsins and their inhibitors was significantly higher in pre-LVAD compared to the HT group and LVAD induced a further increase in the cathepsin system. Significant positive correlations were observed between cardiac expression of cathepsins and their inhibitors as well as inflammatory cytokines. In the pre-LVAD group, a relationship of cathepsins with dilatative etiology and length of hospitalization was found.

Conclusions: A parallel activation of cathepsins and their inhibitors was observed after LVAD support. The possible clinical importance of these modifications is confirmed by their relation with patients' outcome. A better discovery of these pathways could add more insights into the cardiac remodeling during HF.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Cysteine cathepsins. mRNA expression of cysteine cathepsins in cardiac tissue from ESHF patient of pre-LVAD group (n=22), HT control group (n=35) and post-LVAD group (n=30), respectively. Relative expressions (mean value ± SEM) of CatB (A), CatL (B), CatS (C) CatK (D) are shown.
Figure 2
Figure 2
Cysteine cathepsin inhibitors. mRNA expression of cysteine cathepsin inhibitors in cardiac tissue from ESHF patient of pre-LVAD group (n = 22), HT control group (n = 35) and post-LVAD group (n = 30), respectively. Relative expression (mean value ± SEM) of CysB (A) and CysC (B) are shown.
Figure 3
Figure 3
Serine cathepsin system. mRNA expression of serine cathepsin system in cardiac tissue from ESHF patients of pre-LVAD group (n = 22), HT control group (n = 35) and post-LVAD group (n = 30), respectively. Relative expressions (mean value ± SEM) of CatG (A) and SrpA3 (B) are shown.
Figure 4
Figure 4
SrpA3 and HF etiology in pre-LVAD patients. IDC: Idiopathic dilatative cardiomyopathy; IHD: ischemic heart disease.
Figure 5
Figure 5
Cathepsin system and clinical outcome. Correlation between myocardial SrpA3 (A), CatK (B) and CatS (C) and length of hospitalization in pre-LVAD patients.
See this image and copyright information in PMC

References

    1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, 3rd, Moy CS, et al. Heart Disease and Stroke Statistics—2014 Update: a report from the American heart association. Circulation. 2014;129(3):e28–e292. doi: 10.1161/01.cir.0000441139.02102.80. - DOI - PMC - PubMed
    1. Wilson SR, Givertz MM, Stewart GC, Mudge GH., Jr Ventricular assist devices the challenges of outpatient management. J Am Coll Cardiol. 2009;54(18):1647–1659. doi: 10.1016/j.jacc.2009.06.035. - DOI - PubMed
    1. Hall JL, Fermin DR, Birks EJ, Barton PJ, Slaughter M, Eckman P, Baba HA, Wohlschlaeger J, Miller LW. Clinical, molecular, and genomic changes in response to a left ventricular assist device. J Am Coll Cardiol. 2011;57(6):641–652. doi: 10.1016/j.jacc.2010.11.010. - DOI - PMC - PubMed
    1. Muller AL, Dhalla NS. Role of various proteases in cardiac remodeling and progression of heart failure. Heart Fail Rev. 2012;17(3):395–409. doi: 10.1007/s10741-011-9269-8. - DOI - PubMed
    1. Cheng XW, Shi GP, Kuzuya M, Sasaki T, Okumura K, Murohara T. Role for cysteine protease cathepsins in heart disease: focus on biology and mechanisms with clinical implication. Circulation. 2012;125(12):1551–1562. doi: 10.1161/CIRCULATIONAHA.111.066712. - DOI - PubMed

Publication types