Circulating immunoglobulins are not associated with intraplaque mast cell number and other vulnerable plaque characteristics in patients with carotid artery stenosis.

BACKGROUND\nRecently, we have shown that intraplaque mast cell numbers are associated with atherosclerotic plaque vulnerability and with future cardiovascular events, which renders inhibition of mast cell activation of interest for future therapeutic interventions. However, the endogenous triggers that activate mast cells during the progression and destabilization of atherosclerotic lesions remain unidentified. Mast cells can be activated by immunoglobulins and in the present study, we aimed to establish whether specific immunoglobulins in plasma of patients scheduled for carotid endarterectomy were related to (activated) intraplaque mast cell numbers and plasma tryptase levels. In addition, the levels were related to other vulnerable plaque characteristics and baseline clinical data.\nMETHODS AND RESULTS\nOxLDL-IgG, total IgG and total IgE levels were measured in 135 patients who underwent carotid endarterectomy. No associations were observed between the tested plasma immunoglobulin levels and total mast cell numbers in atherosclerotic plaques. Furthermore, no associations were found between IgG levels and the following plaque characteristics: lipid core size, degree of calcification, number of macrophages or smooth muscle cells, amount of collagen and number of microvessels. Interestingly, statin use was negatively associated with plasma IgE and oxLDL-IgG levels.\nCONCLUSIONS\nIn patients suffering from carotid artery disease, total IgE, total IgG and oxLDL-IgG levels do not associate with plaque mast cell numbers or other vulnerable plaque histopathological characteristics. This study thus does not provide evidence that the immunoglobulins tested in our cohort play a role in intraplaque mast cell activation or grade of atherosclerosis.Biopharmaceutic

VEGFR2 Blockade in Murine Vein Grafts Reduces Intraplaque Hemorrhage due to Enhanced Plaque Neovessel Maturation

Vascular Surger

C57BL/6 Nk Cell Gene Complex Crucially Involved in Vascular Remodeling and Intimal Hyperplasia

Vascular Surger

RP105, A Cell Surface TLR4 Signaling Regulator, Enhances Atherosclerotic Plaque Formation

Atherosclerosi

Interferon Regulatory Factors 3 and 7 Regulate Vein Graft Remodeling via Tumor Necrosis Factor Induced Macrophage Accumulation

Vascular Surger

Activation of the innate immune system in atherosclerotic disease

Innate immunity is the first line of defence against invading micro-organisms. The family of Toll-like receptors (TLRs) recognizes pathogen-associated molecular patterns (PAMPs) that are carried by the invading micro-organisms. Infectious pathogens have been implicated to play an important role in atherosclerosis. Nowadays, evidence is accumulating that TLRs play an important role in the initiation and progression of atherosclerosis too. A lot is known about the exogenous ligands that are able to activate the TLRs, but it is also known that endogenous ligands have the capacity to activate TLRs when exogenous ligands are absent. Studies on knockout mice, epidemiological studies and even human polymorphism studies confirmed the important role of TLRs in development and progression of atherosclerotic disease. Studies with antagonists against TLR ligands and vaccination studies demonstrated that TLR signaling might be a potential target for intervention in the initiation and progression of atherosclerosis. © 2007 Bentham Science Publishers Ltd

VLDL receptor deficiency enhances intimal thickening after vascular injury but does not affect atherosclerotic lesion area

Department of Human and Clinical Genetics, Leiden University Medical Center, PO Box 9503, 2300 RA Leiden, The Netherlands. The very low density lipoprotein receptor (VLDLR) has been shown to modulate cell migration and foam cell formation in vitro. This suggests a role for the VLDLR in vascular pathology associated with intimal thickening and atherogenesis. In the present paper both intimal thickening and atherosclerosis were studied using VLDLR knockout and transgenic mouse models. The role of the VLDLR in intimal thickening was established in an in vivo model for vascular injury. A non-restrictive cuff was placed around the femoral artery of VLDLR deficient (VLDLR-/-), heterozygous deficient (VLDLR+/-) and wild type (WT) mice. Intimal thickening was assessed after 3 weeks by determining the intima to media (I/M) volume ratio. Both VLDLR-/- (I/M ratio 42%) and VLDLR+/- (I/M ratio 40%) mice showed a significant increase as compared with WT littermates (I/M ratio 25%). The effect of VLDLR deficiency on atherosclerosis was examined in VLDLR-/- mice on an LDLR deficient (LDLR-/-) background. In addition, we assessed whether increased endothelial VLDLR expression levels affect atherosclerotic lesion formation. Therefore, atherosclerosis was studied in LDLR deficient mice that over express the VLDLR in endothelial cells (PVL, LDLR-/-). Both VLDLR deficiency and endothelial VLDLR over expression did not affect the atherosclerotic lesion size. Interestingly, VLDLR-/-, LDLR-/- mice showed a high incidence of necrosis in both fatty streaks and atherosclerotic plaques as compared with LDLR-/- mice (75 vs. 0% and 76 vs. 45%, respectively). In conclusion, deficiency for the VLDLR profoundly increased intimal thickening after vascular injury

TLR4 Is a Potential Local Therapeutic Target Against Vein Graft Disease

Vascular Surger