PURPOSE OF REVIEW: The purpose of this review is to summarize evidence about the effects that mast cell mediators can exert on the cholesterol efflux-inducing function of high density lipoproteins (HDL). RECENT FINDINGS: Subendothelially located activated mast cells are present in inflamed tissue sites, in which macrophage foam cells are also present. Upon activation, mast cells degranulate and expel 2 major neutral proteases, chymase and tryptase, and the vasoactive compound histamine, all of which are bound to the heparin-proteoglycan matrix of the granules. In the extracellular fluid, the proteases remain heparin-bound and retain their activities, whereas histamine dissociates and diffuses away to reach the endothelium. The heparin-bound mast cell proteases avidly degrade lipid-poor HDL particles so preventing their ability to induce cholesterol efflux from macrophage foam cells. In contrast, histamine enhances the passage of circulating HDL through the vascular endothelium into interstitial fluids, so favoring HDL interaction with peripheral macrophage foam cells and accelerating initiation of macrophage-specific reverse cholesterol transport. SUMMARY: Mast cells exert various modulatory effects on HDL function. In this novel tissue cholesterol-regulating function, the functional balance of histamine and proteases, and the relative quantities of HDL particles in the affected microenvironment ultimately dictate the outcome of the multiple mast cell effects on tissue cholesterol content.
PURPOSE OF REVIEW: The purpose of this review is to summarize evidence about the effects that mast cell mediators can exert on the cholesterol efflux-inducing function of high density lipoproteins (HDL). RECENT FINDINGS: Subendothelially located activated mast cells are present in inflamed tissue sites, in which macrophage foam cells are also present. Upon activation, mast cells degranulate and expel 2 major neutral proteases, chymase and tryptase, and the vasoactive compound histamine, all of which are bound to the heparin-proteoglycan matrix of the granules. In the extracellular fluid, the proteases remain heparin-bound and retain their activities, whereas histamine dissociates and diffuses away to reach the endothelium. The heparin-bound mast cell proteases avidly degrade lipid-poor HDL particles so preventing their ability to induce cholesterol efflux from macrophage foam cells. In contrast, histamine enhances the passage of circulating HDL through the vascular endothelium into interstitial fluids, so favoring HDL interaction with peripheral macrophage foam cells and accelerating initiation of macrophage-specific reverse cholesterol transport. SUMMARY: Mast cells exert various modulatory effects on HDL function. In this novel tissue cholesterol-regulating function, the functional balance of histamine and proteases, and the relative quantities of HDL particles in the affected microenvironment ultimately dictate the outcome of the multiple mast cell effects on tissue cholesterol content.
Authors: Ilona Kareinen; Marc Baumann; Su Duy Nguyen; Katariina Maaninka; Andrey Anisimov; Minoru Tozuka; Matti Jauhiainen; Miriam Lee-Rueckert; Petri T Kovanen Journal: J Lipid Res Date: 2018-03-26 Impact factor: 5.922
Authors: Su Duy Nguyen; Katariina Maaninka; Jani Lappalainen; Katariina Nurmi; Jari Metso; Katariina Öörni; Mohamad Navab; Alan M Fogelman; Matti Jauhiainen; Miriam Lee-Rueckert; Petri T Kovanen Journal: Arterioscler Thromb Vasc Biol Date: 2015-12-17 Impact factor: 8.311