Cardiac fibrosis: An abnormal thickening of the heart wall leading to congestive heart failure, was not only halted but also reversed by a Caveolin-1 surrogate peptide (CSD) in a preclinical model, say researchers at the Medical University of South Carolina (MUSC) in an article published online by Laboratory investigation.
CSD was able to decrease the fibrotic ventricular wall thickness and improve heart function with no toxicity and minimal off-target effects.
The MUSC research team included pulmonary fibrosis investigators Stanley Hoffman, Ph.D., and Elena V. Tourkina, Ph.D., who had previously shown caveolin-1’s anti-fibrotic properties in the skin and lung. For this project, they joined forces with MUSC congestive heart failure researchers in the laboratory of Dhandapani Kuppuswamy, Ph.D., to show that caveolin-1’s anti-fibrotic properties in skin and lung also hold in yet another organ: the heart.
It is noted that skin and lung cells producing excess collagen in Scleroderma leading to fibrosis were deficient in Caveolin-1. Supplementing these cells with a Caveolin-1 surrogate peptide a truncated version of the original compound, showed a reversal of fibrosis.
MUSC has obtained a patent to test CSD on fibrotic diseases across organs which they have licensed to Lung Therapeutics, Inc. The company intends to support research involving CSD and fibrosis in the Hoffman and Kuppuswamy laboratories.
Kuppuswamy’s laboratory focuses on hypertrophic overgrowth and profibrogenic signaling of the cardiac muscle in pressure overload. Fibrosis that develops under these conditions is detrimental to the heart’s pumping efficiency as it causes a stiffer and less compliant cardiac muscle, leading to the progression of congestive heart failure.
Currently, there are no therapeutic options for congestive heart failure that specifically target the causative cardiac fibrosis. According to CDC, heart failure affects almost 6 million Americans and half of those with heart failure die within 5 years of diagnosis.
Researchers used a transverse aortic constriction mouse model to mimic the cardiac fibrosis in the mouse model and created pressure overload hypertrophy that then led to the development of fibrosis. Treatment with CSD not only halted the progression of the cardiac fibrosis but also led to its reversal with improved ventricular function.
Although promising, these findings are preliminary- only reflecting outcomes in mice. Researchers are planning to run larger preclinical studies using the same approach to generate more definitive data and if all goes as expected to move forward to the large-animal studies necessary to take a compound forward into the clinical trial.
Researchers also note that they are testing CSD in different congestive heart failure model, the angiotensin II infusion model, which also affects the kidneys.
Fibrotic diseases are related to each other no matter the affected organ. In our case, we were studying lung and skin fibrosis,”
The co-authors thank the MUSC College of Medicine Enhancement of Team Science (COMETS) for helping support this work. Without this support, this work would not have been possible.