Development of Abdominal Aortic Aneurysm Is Decreased in Mice with Plasma Phospholipid Transfer Protein Deficiency

Abstract

Plasma phospholipid transfer protein (PLTP) increases the circulating levels of proatherogenic lipoproteins, accelerates blood coagulation, and modulates inflammation. The role of PLTP in the development of abdominal aortic aneurysm (AAA) was investigated by using either a combination of mechanical and elastase injury at one site of mouse aorta (elastase model) or continuous infusion of angiotensin II in hyperlipidemic ApoE-knockout mice (Ang II model). With the elastase model, complete PLTP deficiency was associated with a significantly lower incidence and a lesser degree of AAA expansion. With the Ang II model, findings were consistent with those in the elastase model, with a lower severity grade in PLTP-deficient mice, an intermediate phenotype in PLTP-deficient heterozygotes, and a blunted effect of the PLTP-deficient trait when restricted to bone marrow-derived immune cells. The protective effect of whole-body PLTP deficiency in AAA was illustrated further by a lesser degree of adventitia expansion, reduced elastin degradation, fewer recruited macrophages, and less smooth muscle cell depletion in PLTP-deficient than in wild-type mice, as evident from comparative microscopic analysis of aorta sections. Finally, cumulative evidence supports the association of PLTP deficiency with reduced expression and activity levels of matrix metalloproteinases, known to degrade elastin and collagen. We conclude that PLTP can play a significant role in the pathophysiology of AAA.

Phospholipid Transfer Protein Destabilizes Mouse Atherosclerotic Plaque

“…[9][10][11] Systemic PLTP deficiency in mice is also associated with a reduced thrombotic response 12 and reduced abdominal aortic aneurysm. 13 In rabbits, overexpression of PLTP-increased atherosclerotic lesions after a high-fat diet feeding when compared with controls. 14 In general, PLTP is a risk factor of atherosclerosis in animal models.…”

Plasma phospholipid transfer protein (PLTP) modulates adaptive immune functions through alternation of T helper cell polarization

“…22,23 Finally, in a recent study from our group, the expression level of IL-6 and the number of infiltrating macrophages in aortic tissue after the induction of experimental aneurysm were lower in PLTP-deficient mice than in WT mice, providing additional support for the anti-inflammatory effect of PLTP deficiency in mice. 24 With regard to human studies, Cheung 11 and PLTP activity was found to be significantly increased in patients with bacterial infections and systemic inflammation. 25 In the present work, we observed that neither the total WBC counts nor the CD3 1 -cell subpopulations were modified in a PLTP-deficient context.…”

Allergic lung inflammation promotes atherosclerosis in apolipoprotein E-deficient mice

“…Collagen content, elastin fragmentation and media SMC accumulation were graded according to the grading keys that were described previously. 29,30 CD31-positive microvessels, Ki67-positive cells, T cells, mast cells, and apoptotic cells were counted manually in a blinded fashion and presented as numbers per aortic arch section. Images of the relative macrophage and MHC-II contents within the aortas were captured by a Microscope VS120 Whole Slide Scanner (Olympus) and quantified by measuring the immunostaining signal-positive areas using computer-assisted image analysis software (Image-Pro Plus; Media Cybernetics, Bethesda, MD).…”