Reddy Srinivasa T, Anantharamaiah G M, Navab Mohamad, Hama Susan, Hough Gregory, Grijalva Victor, Garber David W, Datta Geeta, Fogelman Alan M
Division of Cardiology, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California 90095-1679, USA.
Expert Opin Investig Drugs. 2006 Jan;15(1):13-21. doi: 10.1517/13543784.15.1.13.
Cholesterol can promote inflammation by its ability to stimulate the production of reactive oxygen species that result in the formation of pro-inflammatory oxidised phospholipids. High-density lipoproteins (HDLs) are part of the innate immune response and can be either pro- or anti-inflammatory independently of plasma HDL-cholesterol levels. During systemic inflammation as occurs with atherosclerosis, Apolipoprotein A-I can be altered, reducing its ability to promote reverse cholesterol transport and HDL can become pro-inflammatory. Amphipathic peptides with either a class A amphipathic helix (D-4F) or a class G* amphipathic helix (D-[113-122]apoJ), or even those that are too small to form a helix (KRES and FREL) have some similar characteristics. Their interaction with lipids leads to a reduction in lipoprotein-lipid hydroperoxides that releases HDL-associated antioxidant enzymes, such as paraoxonase, therefore providing antiatherosclerosis and anti-inflammatory activity. In addition, the peptide D-4F stimulates the formation and cycling of pre-beta HDL. These amphipathic peptides appear to have therapeutic potential as oral agents.
胆固醇能够通过刺激活性氧的产生来促进炎症，活性氧会导致促炎性氧化磷脂的形成。高密度脂蛋白（HDL）是先天性免疫反应的一部分，并且可以独立于血浆HDL-胆固醇水平而具有促炎或抗炎作用。在诸如动脉粥样硬化时发生的全身炎症期间，载脂蛋白A-I可能会发生改变，降低其促进胆固醇逆向转运的能力，并且HDL可能会变得具有促炎性。具有A类两亲性螺旋（D-4F）或G*类两亲性螺旋（D-[113-122]载脂蛋白J）的两亲性肽，甚至那些太小而无法形成螺旋的肽（KRES和FREL）都具有一些相似的特性。它们与脂质的相互作用会导致脂蛋白-脂质氢过氧化物减少，从而释放出与HDL相关的抗氧化酶，如对氧磷酶，因此具有抗动脉粥样硬化和抗炎活性。此外，肽D-4F会刺激前β-HDL的形成和循环。这些两亲性肽似乎具有作为口服药物的治疗潜力。
