I am trying to measure markers of early fibrosis in heart tissue of spontaneously hypertensive heart failure rats. Echocardiographic data shows that my drug treatment improved diastolic dysfunction, while untreated animal group had a prolonged IVRT (a marker of diastolic dysfunction).
Since one possible contributor to diastolic dysfunction is fibrosis, I will like to probe for markers of fibrosis (preferably early fibrosis) in the treated versus untreated animal groups. I am thinking in the line of Collagen I or III and fibronectin?? Does anyone has other ideas of what could be a great marker of fibrosis or diastolic dysfunction?
Are there other factors that could contribute to diastolic function that I can probe at the molecular levels??
Meanwhile the animals still had normal ejection fraction so they are not yet in the decompensated heart failure stage.
Thank you.
B.
Hi.. PINP, PIIINP,Glactin 3 and ST2 are probably the best marker of cardiac fibrosis... Immunohistochemical test with monoclonal antibody to detect the amount of type 1and type III collagen may be also helpful.. Thanks.. You can follow the following links
http://www.onlinejcf.com/article/S1071-9164(07)00584-2/abstract
Hello Biswajit and Anna, I do not have serum samples of these animals, so I may not be able to measure the PINP and PIIINP. I have only the heart tissue samples so I am planning to probe for collagen I and III by western blotting the heart tissue lysates. Does this sound reasonable?
You could check αSMA. Cardiac injury triggers cardiac fibroblasts to be differentiated into myofibroblasts. They are not found in healthy myocardium and only appear following cardiac injury. Myofibroblasts have a key role in reparative fibrosis and colllagen deposition in the infarcted heart. Moreover, αSMA is not typically expressed in quiescent healthy cardiac fibroblasts.
Cardiac mRNA and protein expression of brain natriuretic peptide (BNP), galectin-3 (Gal-3), connective tissue growth factor (CTGF), osteopontin (OPN) and transforming growth factor β-1. 'Ratio between collagen I and III' - it is a good idea from Anna Folino.
Myocyte size, interstitial collagen and capillary density - best way to measure fibrosis. Please read Suzuki G. - Circulation - 2002. MMP 2, 9, PICP, NGAL, Thrombosponin 2 (TSP 2), miR 21, miR 24, miR 212/132 is best marker for fibrosis.
thank you everyone for your suggestions. I will be looking at collagen I and collagen III as well as fibronectin. I appreciate your perspectives.
Additional information maybe helpful.
Please see ANMCO/ELAS/SIBioC Consensus Document published in May 2017.
Point 1. There are still some doubts on efficiency, prognostic role, and cost-effectiveness of biomarkers of cardiac remodelling and myocardial fibrosis, even if many studies have been published recently.
Point 2. Considering the wide range of biomarkers of cardiac remodelling and myocardial fibrosis, the clinician should direct his decision remembering the analytical characteristics of the assay, the efficiency and prognostic effectiveness of the biomarker also in relation to patients’ setting, possible confounding variables, co-morbidities and costs.
Point 3. Novel biomarkers and multi-markers models
The search is still open for novel biomarkers useful for prognosis and guide therapy in HF patients. Promising candidate biomarker may be: growth differential factor-15 (GDF-15), carbohydrate antigen-125 (CA-125), C-terminal pro-vasopressin (copectin), mid-regional pro-adrenomedullin (MR-proADM), NEP and orexin. Some of these molecules have been utilized for many years as tumour-markers (CA-125), neuro-hormones (copeptin, MR-proADM) or inflammatory markers (GDF-15) in clinical practice.
https://academic.oup.com/eurheartjsupp/article/19/suppl_D/D102/3792740/ANMCO-ELAS-SIBioC-Consensus-Document-biomarkers-in
Big project by F. Zannand.
All about fibrosis in HF patients.
http://www.fibrotargets.eu/
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