Advantages:
- ALOX5 expression promotes the synthesis of inflammation resolving factors after infarction
- ALOX5 deficiency is linked with increased inflammatory signaling and poor outcomes
- ALOX5 represents a novel potential therapeutic target to treat heart failure
Summary:
Chronic inflammation is a prime determinant for ischemic and non-ischemic heart failure (HF). After an injury to the heart, two leukocyte-directed responses are activated to regulate the myocardium: proinflammatory mediators (PIMs) initiate an inflammatory response to clear injured/ dead cardiomyocytes; long-chain fatty acid-derived specialized pro-resolving mediators (SPMs) clear inflammation and prevent myocardium damage.
Our researchers discovered that activated leukocytes express arachidonate 5-Lipoxygenase (ALOX5) which is critically involved in the biosynthesis of SPMs (e.g. such as lipoxins, MaR1, PD1, and RvD5 ) in the infarcted heart to clear inflammation and promote cardiac repair. ALOX5 deficiency reduced the levels of SPMs, promoted defective TGF-b signaling with marked fibroblasts disposition to myofibroblasts, all of which impaired the resolution of inflammation and cardiac repair. These findings are indicative of a critical role of ALOX5 as novel therapeutic target in myocardium. Increasing ALOX5 levels after infarction can aid in resolving inflammation and promoting cardiac repair to prevent subsequent heart failure.
Deletion of ALOX5 in mice decreased post-MI survival, worsened cardiac function, and structure in acute and chronic HF.
Desired Partnerships:
- License
- Sponsored Research
- Co-Development