Our results indicate that TK-modified MSCs provide enhanced protection against cardiac injury, apoptosis and inflammation, and promote neovascularization after MI, leading to cardiac function improvement.
Using an MI mouse model, we then examined the in vivo effects of human TK gene adenoviral vector (Ad.hTK) administration on the number of CD34(+)Flk-1(+) progenitors in the peripheral circulation, heart tissue, extent of vasculogenesis, and heart function.
These data provide the first direct evidence that tissue kallikrein protects against acute-phase MI by promoting neovascularization, restoring regional blood flow and improving cardiac function through the kinin B2 receptor-Akt-GSK-3beta and VEGF signalling pathways.
A chronically activated transgenic kallikrein kinin system with expression of human kallikrein-1 gene counteracts the progression of left ventricular contractile dysfunction after experimental myocardial infarction.
Rats were subjected to coronary artery ligation to induce MI, and adenovirus carrying the human tissue kallikrein or luciferase gene was injected into the tail vein at 1 week after surgery.
These and other effects, make the human tissue kallikrein (hKLK1) gene a candidate gene with respect to BP regulation as well as risk of myocardial infarction (MI).