In order to bring you the best possible user experience, this site uses Javascript. If you are seeing this message, it is likely that the Javascript option in your browser is disabled. For optimal viewing of this site, please ensure that Javascript is enabled for your browser.

The free consultation period for this content is over.

It is now only available year-round to ESC Professional Members, Fellows of the ESC, and Young combined Members

Extracellular matrix remodeling in early cardiac fibrosis and diastolic dysfunction

Session Poster Session 5

Speaker Sandra Voss

Event : ESC Congress 2013

  • Topic : basic science
  • Sub-topic : Basic Science - Other
  • Session type : Poster Session

Authors : M Willmer (Bad Nauheim,DE), S Szardien (Bad Nauheim,DE), D Kraft (Bad Nauheim,DE), S Voss (Bad Nauheim,DE), C Troidl (Bad Nauheim,DE), J Hoffmann (Bad Nauheim,DE), C Liebetrau (Bad Nauheim,DE), H Nef (Giessen,DE), C Hamm (Bad Nauheim,DE), H Moellmann (Bad Nauheim,DE)

Authors:
M. Willmer1 , S. Szardien1 , D. Kraft1 , S. Voss1 , C. Troidl1 , J. Hoffmann1 , C. Liebetrau1 , H. Nef2 , C. Hamm1 , H. Moellmann1 , 1Kerckhoff Heart and Thorax Center, Department of Cardiology - Bad Nauheim - Germany , 2Justus-Liebig University Giessen, Medical Clinic I, Cardiology - Giessen - Germany ,

Citation:
European Heart Journal ( 2013 ) 34 ( Abstract Supplement ), 770-771

Background: Half of the patients with congestive heart failure suffer from diastolic dysfunction with persistent left ventricular function (HFpEF). Until today different explanations exist, but the exact mechanism of HFpEF is still unclear. From human biopsies and different animal models it is known that in HFpEF the extracellular matrix underlies remodeling processes with increased fibrosis and disturbance of cardiac architecture. Our study aimed to characterize changes of the extracellular matrix in early cardiac fibrosis and diastolic dysfunction.

Methods: In C57Bl/6-mice, osmotic minipumps were implanted with a continuous infusion of Angiotensin II (Ang, 0.5μg/kg/min) or NaCl (Sham). After assessment of systolic and diastolic parameters using echocardiography at day 7 or 28, mice were euthanized (Ang7d, n=22/Ang28d, n=27/Sham, n=20). Cardiac tissue was investigated with micro array technology, western blot, qRT-PCR and immunohistochemistry.

Results: Echocardiography revealed a reliable induction of diastolic dysfunction with persistent LVEF in the Ang groups (E/E': Sham 25.9±1.0 vs. Ang28d 38.5±4.4; p<0.01). BNP expression was significantly increased (Sham 0.7±0.1 vs. Ang28d 1.9±0.4; p<0.05). Histochemical examination showed a significantly elevated interstitial fibrosis with significant increase of Vimentin positive cardiac fibroblasts. Expressions of Collagen 1, 3, 4, 6 and 14 were increased. By using mRNA micro array technology different targets of the extracellular remodeling process were identified and validated by qRT-PCR. The expressions of the collagen maturation enzyme LOX and of the fibrillogenesis promoting proteins Sparc were significantly increased. Fibromodulin, which is known to regulate collagen fibril diameters, was also elevated (Sham 2.3±0.6 vs. Ang28d 14.5±3.9; p<0.05). Expressions of the Small leucine-rich repeat proteoglycan Decorin and Osteoglycin were reduced after 7 days, while Osteopontin showed significantly elevated expression. Lumican and Asporin were unchanged. The expression of adhesion permitting protein Tenascin C was significantly elevated. Interestingly, expression of the Cartilage Intermediate Layer Protein (CILP), which is only known to take part in the cartilage remodeling process, was clearly increased (Sham 1.9±0.3 vs. Ang28d 8.3±1.9; p<0.01).

Conclusion: The Angiotensin induced cardiac fibrosis was composed by an intensified fibrillogenesis and a changed composition of SLRPs. Furthermore, the significantly elevated expression of CILP suggests a contribution of this extracellular protein to the process of cardiac fibrosis and diastolic dysfunction.

Get your access to resources

Join now
  • 1ESC Professional Members – access all ESC Congress resources 
  • 2ESC Association Members (Ivory, Silver, Gold) – access your Association’s resources
  • 3Under 40 or in training - with a Combined Membership, access all resources
Join now

Our sponsors

ESC 365 is supported by Bayer, Boehringer Ingelheim and Lilly Alliance, Bristol-Myers Squibb and Pfizer Alliance, Novartis Pharma AG and Vifor Pharma in the form of educational grants. The sponsors were not involved in the development of this platform and had no influence on its content.

logo esc

Our mission: To reduce the burden of cardiovascular disease

Who we are