A compendium of the apoA-IMilano biological effects

Obesity is a pathologic condition generated by an energy imbalance, that is, excess caloric consumption, leading to weight gain and metabolic disturbances characterized by adipose tissue inflammation and hyperglycemic conditions. In line with these observations, increasing evidence causally links inflammation, or the molecules and networks integral to inflammatory response, to the development of obesity and the complications that emerge from this pathology, such as cardiovascular, neurologic, respiratory, and metabolic illnesses, as well as sepsis and cancer. Not surprisingly, this chronic and abnormal metabolic background leads to constant derangements in innate and adaptive immunity. It is well known that high-density lipoprotein (HDL) possesses anti-inflammatory and antioxidant properties, and various studies have highlighted an emerging role of HDL in modulating immune function. The efficacy of synthetic HDL (sHDL) containing the recombinant form of apoA-IMilano (sHDL-apoA-IM), originating from the observation that carriers of this mutation have low levels of HDL cholesterol without increased atherosclerosis, has been largely proved in diverse animal models of atherosclerosis; however, the therapeutic use of sHDL-apoA-IM still needs clinical validation. One of the main limitations to the use of recombinant proteins in clinical studies lies in the unsustainable purification costs. Unpurified rice-milk-apoA-IM demonstrated anti-inflammatory and antiatherogenic properties in a mouse model, even though administrated by an unconventional way: by oral gavage. Additionally, recent data have uncovered new therapeutic applications for this sHDL-apoA-IM This review provides an overview of all potential application of sHDL-apoA-IM in some inflammatory-based diseases. SIGNIFICANCE STATEMENT: A recent study demonstrated that oral administration of rice-seed protein extracts containing the apoA-IM (i.e., the milk-apoA-IM) reduced atherosclerosis development in a mouse model. Moreover, the rice-milk-apoA-IM preserved both in vitro and in vivo anti-inflammatory properties, as observed when sHDL-apoA-IM was given by intravascular infusion. Besides, various studies suggested that sHDL-apoA-IM could positively affect other inflammatory-based diseases. Together, these data might represent a new starting point for "sHDL-apoA-IM-based therapies" in chronic degenerative disease.