| Summary |
Cardiovascular and pulmonary diseases are leading causes of morbidity and mortality worldwide. Studies report an inverse correlation between levels of serum high-density lipoprotein (HDL) and the severity of cardiovascular and lung diseases. HDL has also been shown to be anti-inflammatory, anti-atherosclerotic, and anti-oxidative. HDL's cardioprotective functions are well understood through the reverse cholesterol transport process. However, how HDL effects the immune system in the lungs is still unknown. We hypothesize that HDL is critical in preventing pulmonary injury from lipopolysaccharide (LPS) through inhibiting neutrophil (PMN) chemotaxis. While HDL is known to be biologically protective, it has also been reported that HDL can become dysfunctional (D-HDL) in chronic inflammatory diseases. HDL is characterized as dysfunctional when it does not perform its protective mechanisms. It has been challenging to study D-HDL, in part, because D-HDL is found in specific patient populations commonly burdened with comorbidities and subsequent medications. Apolipoprotein A-I (apoA-I), the major protein component of HDL, is primarily responsible for HDL's beneficial properties. There are apoA-I mimetic peptides, such as L-4F, available to study the biological properties of HDL in both in vitro and in vivo models. However, there is no such research tool available to study D-HDL. Therefore, to better understand how D-HDL differs from HDL, we also sought to design a D-HDL mimetic peptide that can be used to examine the biological mechanisms of how HDL and D-HDL differ. |
