NU 2020-159
INVENTORS Guillermo Oliver* Xialoei Liu
SHORT DESCRIPTION A novel approach to treating cardiovasculature disease
BACKGROUND Although little is known about the role of cardiac lymphatics in the healthy or failing heart, a growing body of evidence indicates that improved cardiac lymphatic vessel growth and function could be a novel therapeutic approach for combatting cardiovascular disease. Myocardial infarction (MI), the most common heart injury, is a life-threatening condition resulting in tissue damage and massive cardiomyocyte (CM) death. This in turn leads to the formation of fibrotic tissue, pathological remodeling and eventually heart failure. Defective lymphatic function has been linked to cardiovascular diseases for some time. Recent findings suggest that abnormal cardiac lymph flow promotes cardiac edema and that MI is a trigger for the production of new cardiac lymphatics. Other reports indicate that naturally or therapeutically stimulated lymphangiogenesis correlates with improved systolic function after MI by facilitating the resolution of myocardial edema and inflammation and by delaying atherosclerotic plaque formation. These new findings indicate that the stimulation of lymphangiogenesis in an infarcted heart could be a valuable therapeutic approach to improving cardiac function and preventing adverse cardiac remodeling.
ABSTRACT Northwestern researchers have identified that reelin (RELN) protein produced by cardiac-associated lymphatic endothelial cells (LECs) controls cardiomyocyte (CM) proliferation and survival during cardiac regeneration after neonatal and adult myocardial infarction. Through preliminary in vitro and in vivo mouse studies, they have observed that RELN is a key component of this process, probably via the Itgb1 signalling pathway. LEC-specific Reln-null mouse embryos develop smaller hearts, that RELN is required for efficient heart repair and function after neonatal myocardial infarction, and that cardiac delivery of RELN using collagen patches improves heart function in adult mice after myocardial infarction by a cardioprotective effect. These results highlight a lymphoangiocrine role of LECs during cardiac development and injury response, and identify RELN as an important mediator of this function, suggestive that it may be a valuable therapeutic approach to improve cardiac function in humans.
APPLICATIONS
ADVANTAGES
PUBLICATIONS Liu X, De la Cruz E, Gu X et al. (2020) Lymphoangiocrine signals promote cardiac growth and repair. Nature. 588: 705.
IP STATUS Provisional applications have been filed.