Novel Therapy for Atherosclerosis Using Recombinant Immunotoxin Against Folate Receptor β-Expressing Macrophages.

Background: Folate receptor β (FRβ) is induced during macrophage activation. A recombinant immunotoxin consisting of the truncated Pseudomonas exotoxin A (PE38) conjugated to an anti-FRβ antibody (anti-FRβ-PE38) has been reported to kill activated macrophages in inflammatory diseases. To elucidate the effect of an immunotoxin targeting FRβ on atherosclerosis, we determined the presence of FRβ-expressing macrophages in atherosclerotic lesions and administered the FRβ immunotoxin in apolipoprotein E-deficient mice.

Waon therapy upregulates Hsp90 and leads to angiogenesis through the Akt-endothelial nitric oxide synthase pathway in mouse hindlimb ischemia.

Background: Thermal therapy, namely Waon therapy, has previously been reported to regulate nitric oxide (NO) and endothelial NO synthase (eNOS) and augment ischemia-induced angiogenesis in mice and improve limb ischemia in patients with peripheral artery disease. The aim of this study was to clarify the precise mechanism by which Waon therapy augments angiogenesis in mice with hindlimb ischemia.

Methods And Results: Unilateral hindlimb ischemia was induced in apolipoprotein E-deficient mice and Waon therapy was performed for 5 weeks.

Loss of clusterin limits atherosclerosis in apolipoprotein E-deficient mice via reduced expression of Egr-1 and TNF-α.

Aim: Whether clusterin/apolipoprotein J is antiatherogenic or proatherogenic is controversial. We reported that clusterin was markedly induced in media and neointima after vascular injury and that reduced clusterin expression reduced the proliferation of vascular smooth muscle cells (VSMCs), which induced G1 arrest via p53 and p21. The purpose of this study was to investigate the physiological function of clusterin in atherosclerosis using double-knockout mice (D-KO) of apolipoprotein E-deficient mice (apoE-KO) and clusterin-deficient mice (CLU-KO).

Deficiency of clusterin inhibits neointimal hyperplasia after vascular injury.

Aim: Increased clusterin mRNA and protein levels have been detected in various tissues undergoing stress, and we previously reported that clusterin is markedly induced in media and neointima following vascular injury. The present study therefore investigated the impact of clusterin on neointimal hyperplasia following vascular injury.

Methods And Results: As compared with wild-type mice, clusterin knockout mice (clusterin-KO) demonstrated a significant decrease of the intima/media ratio 4 weeks after cuff placement.

Tacrolimus-eluting stent inhibits neointimal hyperplasia via calcineurin/NFAT signaling in porcine coronary artery model.

Aims: The purpose is to elucidate the mechanism by which a newly developed tacrolimus-eluting stent (TES) prevents neointimal hyperplasia after stenting.

Methods And Results: The three major coronary arteries in juvenile swine were randomized to implantation of either a TES or bare metal stent (BMS). Twelve weeks after stenting, the TES showed 29% less neointimal area than the BMS.

Relationship between hyperglycemia and coronary vascular resistance in non-diabetic patients.

Background: Hyperglycemia upon hospital admission in patients with acute myocardial infarction is associated with the no-reflow phenomenon after successful reperfusion, and increased mortality. However, the mechanism underlying this phenomenon remains unclear. Therefore, the aim of this study was to characterize coronary hemodynamics in a homogenous group of non-diabetic patients without coronary artery disease.

The long-term effect of angiotensin II type 1a receptor deficiency on hypercholesterolemia-induced atherosclerosis.

Angiotensin II type 1 receptor may contribute to atherogenesis by facilitating the proliferative and inflammatory response to hypercholesterolemia. In the present study, we investigated the long-term effect of angiotensin II type 1a receptor (AT1a) deficiency on hypercholesterolemia-induced atherosclerosis by the use of AT1a-knockout (AT1a-KO) mice and apolipoprotein E-knockout (apoE-KO) mice. AT1a-KO were crossed with apoE-KO, generating double-knockout (D-KO) mice.

Adiponectin is a better predictor of endothelial function of the coronary artery than HOMA-R, body mass index, immunoreactive insulin, or triglycerides.

Background: Previous studies have demonstrated that decreased levels of circulating adiponectin correlate with endothelial dysfunction in peripheral arteries. However, the relationship between adiponectin levels and endothelial function in coronary arteries remains unclear. The goal of the present study was to determine whether circulating adiponectin concentrations are a useful predictor of coronary endothelial function.

Association between Toll-like receptors and the extent and severity of coronary artery disease in patients with stable angina.

Objectives: Toll-like receptors mediate the innate immune response triggered by pathogen-associated molecular patterns, and atherosclerosis can be considered a state of chronic inflammation whereby immune system cells accumulate within the intima of the arterial wall. The goal of this study was to determine the relation of Toll-like receptors to the extent and severity of coronary artery disease.

Methods: Angiographic vessel score and Gensini score were used to evaluate the extent and severity of coronary atherosclerosis.

Repeated thermal therapy up-regulates endothelial nitric oxide synthase and augments angiogenesis in a mouse model of hindlimb ischemia.

Background: Nitric oxide (NO), constitutively produced by endothelial NO synthase (eNOS), plays roles in angiogenesis. Having reported that thermal therapy up-regulated the expression of arterial eNOS in hamsters, we investigated whether this therapy increased angiogenesis in mice with hindlimb ischemia.

Methods And Results: Unilateral hindlimb ischemia was induced in apolipoprotein E-deficient mice, which were divided into control and thermal therapy groups.