2020-782 FULL-LENGTH CILP AS A BIOMARKER FOR CARDIAC FIBROSIS

SUMMARY

UCLA researchers in the Department of Internal Medicine, Cardiology have identified a circulating biomarker for diagnosing cardiac fibrosis.

BACKGROUND

Cardiac fibrosis is a pathological process associated with various forms of heart diseases that contribute to impaired heart function, development of irregular heartbeat, and ultimately heart failure. Cardiac fibroblasts are primarily responsible for maintaining the structural integrity of the heart by regulating the synthesis of extracellular matrix (ECM). Acute cardiac stress and/or increased cardiac load can initiate the development of myocardial fibrosis which is characterized by excessive secretion of ECM proteins that contribute to scar tissue and stiffening of the heart muscles. Currently, limited treatment options exist for the reversal of cardiac fibrosis, and available therapies for heart failure are ineffective at preventing the formation of scar tissue. Identification of circulating biomarkers would serve as a non-invasive clinical tool for determining the presence, extent, and progression of fibrosis in cardiac patients

INNOVATION

UCLA researchers in the Department of Internal Medicine, Cardiology identified the levels of latent transforming growth factor-β binding protein 2 (Ltbp2), cartilage oligomeric matrix protein (COMP), and cartilage intermediate layer protein 1 (CLIP) significantly change in vitro upon stimulation with transforming growth factor-β (TGF- β). Additionally, they showed that these proteins localize to the fibrotic areas in vivo. They conducted a comprehensive biochemical analysis on a group of heart failure patients and healthy donors and observed that circulating levels of CLIP decreased significantly in patients with heart failure compared to healthy patients. The identification of this biomarker may facilitate the detection of cardiac fibrosis in patients. Thus, CLIP can be used as a potential prognostic biomarker for diagnosing cardiac fibrosis.

POTENTIAL APPLICATIONS

• Biomarker for the detection of cardiac fibrosis, alone or in combination with a panel of other markers.
• Biomarker for detection of ischemic heart failure

ADVANTAGES:

• Non-invasive diagnosis
• The biomarker can be easily detected using standard biochemical assays, including ELISA

DEVELOPMENT-TO-DATE

This invention has been developed and tested in heart failure patients and healthy donors.

Related Papers (from the inventors only)

• Park S, Ranjbarvaziri S, Zhao P, Ardehali R. Cardiac Fibrosis Is Associated With Decreased Circulating Levels of Full-Length CILP in Heart Failure. JACC Basic Transl Sci. 2020 Apr 15;5(5):432-443. doi: 10.1016/j.jacbts.2020.01.016. PMID: 32478206; PMCID: PMC7251193.
• Park S, Ranjbarvazirj S, Lay FD, Zhao P, Miller MJ, Dhaliwal JS, Huertas-Vazquez A, Wu X, Qiao R, Soffer JM, Mikkola HKA, Lusis AJ, Ardehali R. Genetic regulation of fibroblast activation and proliferation in cardiac fibrosis. Circulation. 2018;138:1224-35. PMID: 29950403.