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Updated: Jun 22, 2025
Minimally Invasive Transverse Aortic Constriction in Mice
Published on: March 14, 2017
Treatment with αvβ3-integrin-specific 29P attenuates pressure-overload induced cardiac remodelling after transverse
Alexandra Njegić1,2, Lina Laid2, Min Zi2
1Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom.
Insights
Targeting integrin αvβ3 with a novel therapeutic agent significantly improved cardiac function and reduced detrimental tissue remodeling in a mouse model of heart failure, offering a potential new treatment strategy.
Area of Science:
- Cardiovascular Research
- Integrin Biology
- Pharmacology
Background:
- Heart failure presents a significant global health challenge with limited therapeutic advancements.
- Integrin targeting is established in other diseases but its role in heart failure is underexplored.
Purpose of the Study:
- To investigate the cardioprotective potential of a novel, orally available, αvβ3-specific RGD-mimetic in a pressure-overload heart failure model.
Main Methods:
- Male mice underwent transverse aortic constriction (TAC) and were treated with the αvβ3-specific agent or vehicle.
- Cardiac function and structure were assessed via echocardiography at 3 weeks post-TAC.
- Tissue analysis and RNA sequencing were performed to evaluate molecular and cellular changes.
Main Results:
- Treatment significantly restored cardiac function, including fractional shortening and ejection fraction.
- The agent reduced cardiomyocyte hypertrophy and interstitial fibrosis, key features of heart failure.
- RNA sequencing revealed alterations in pathways related to metabolism, hypertrophy, and basement membrane formation.
Conclusions:
- Targeting αvβ3 with the novel agent attenuates pressure-overload induced cardiac hypertrophy and fibrosis.
- This presents a promising new therapeutic strategy for treating heart failure.
Abstract:
Heart failure remains one of the largest clinical burdens globally, with little to no improvement in the development of disease-eradicating therapeutics. Integrin targeting has been used in the treatment of ocular disease and cancer, but little is known about its utility in the treatment of heart failure. Here we sought to determine whether the second generation orally available, αvβ3-specific RGD-mimetic, 29P , was cardioprotective. Male mice were subjected to transverse aortic constriction (TAC) and treated with 50 μg/kg 29P or volume-matched saline as Vehicle control. At 3 weeks post-TAC, echocardiography showed that 29P treatment significantly restored cardiac function and structure indicating the protective effect of 29P treatment in this model of heart failure. Importantly, 29P treatment improved cardiac function giving improved fractional shortening, ejection fraction, heart weight and lung weight to tibia length fractions, together with partial restoration of Ace and Mme levels, as markers of the TAC insult. At a tissue level, 29P reduced cardiomyocyte hypertrophy and interstitial fibrosis, both of which are major clinical features of heart failure. RNA sequencing identified that, mechanistically, this occurred with concomitant alterations to genes involved molecular pathways associated with these processes such as metabolism, hypertrophy and basement membrane formation. Overall, targeting αvβ3 with 29P provides a novel strategy to attenuate pressure-overload induced cardiac hypertrophy and fibrosis, providing a possible new approach to heart failure treatment.
