Objectives-Enhanced osteoclastogenesis, increased bone resorption, and osteoporosis have been reported in osteoprotegerin-deficient (OPG (Ϫ/Ϫ)) mice. OPG (Ϫ/Ϫ) mice available in Japan usually do not show vascular calcification. We have found that arterial calcification can be quickly induced by a simple procedure in OPG (Ϫ/Ϫ) mice. Methods and Results-Male OPG (Ϫ/Ϫ), OPG (ϩ/Ϫ), and OPG (ϩ/ϩ) mice were fed a high phosphate diet from 6 to 10 weeks after birth, and then 1␣,25-dihydroxyvitamin D3 (calcitriol) was injected for 3 days. We found that severe calcification developed in the media of the aorta in OPG (Ϫ/Ϫ) mice. Under electron microscopy, calcium deposits were observed in the cytoplasm and extracellular matrix of vascular smooth muscle cells (VSMCs Key Words: osteoprotegerin Ⅲ alkaline phosphate Ⅲ vascular smooth muscle cells Ⅲ calcium deposits V ascular calcification, which is frequently observed in patients with end-stage renal disease, diabetes, aging, and osteoporosis, can also lead to cardiovascular diseases and even sudden death. 1-3 Until recently, vascular calcification was considered to be a passive process that occurred as a nonspecific response to tissue injury or necrosis. Now it is becoming increasingly clear that vascular calcification is an actively regulated process that resembles bone metabolism and involves alkaline phosphatase (ALP) and other bonerelated proteins. 4 -7 Osteoprotegerin (OPG) is abundantly produced by osteoblasts at the bone surface and inhibits osteoclast activity, working as a key regulator of bone homeostasis. 8,9 Since it has been reported that OPG (Ϫ/Ϫ) mice exhibit severe osteoporosis attributable to enhanced osteoclastogenesis, OPG is considered to be a protective factor in bone metabolism. 10,11 In the vasculature, the function of OPG is unknown because it is unclear whether vascular calcification takes place in OPG (Ϫ/Ϫ) mice or not. 10,11 Moreover, it was reported that the serum OPG level is associated with the presence and severity of coronary artery disease (CAD). 12 It remains to be clarified whether OPG is involved in the progression of CAD or whether the upregulation of serum OPG concentration is a compensatory mechanism. ALP is a crucial enzyme for initiating mineralization in bone and is present in systemic arteries, arterioles, and some capillaries. 13 It is possible that this enzyme plays a role in arterial calcification by the same mechanism of action as that in bone. 14 Activation of ALP in the arterial wall may result in enhanced vascular calcification.It is well known that either an elevated serum phosphate level or treatment with high doses of vitamin D induces vascular calcification in animal models as well as in humans. 15,16 In the present study, using OPG (Ϫ/Ϫ) mice, we established a mouse model in which arterial calcification can be quickly induced by treatment with a high phosphate diet plus 1␣,25-dihydroxyvitamin D3 (calcitriol) injection, and this model allowed us to perform detailed pathological and biochemical examinations at desired tim...

Abdominal aortic aneurysms (AAAs), which commonly occur among elderly individuals, are accompanied by a risk of rupture and subsequent high mortality. Establishment of medical therapies for the prevention of AAAs requires further understanding of the molecular pathogenesis of this condition. This report details the possible involvement of Osteoprotegerin (OPG) in the prevention of AAAs through inhibition of Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In CaCl2-induced AAA models, both internal and external diameters were significantly increased with destruction of elastic fibers in the media in Opg knockout (KO) mice, as compared to wild-type mice. Moreover, up-regulation of TRAIL expression was observed in the media by immunohistochemical analyses. Using a culture system, both the TRAIL-induced expression of matrix metalloproteinase-9 in smooth muscle cells (SMCs) and the chemoattractive effect of TRAIL on SMCs were inhibited by OPG. These data suggest that Opg may play a preventive role in the development of AAA through its antagonistic effect on Trail.

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BACKGROUND Patients with vasospastic angina (VSA) sometimes experience prolonged chest symptoms. The clinical characteristics of these patients have not been clarified. AIM To investigate the clinical characteristics of prolonged VSA patients. METHODS This study included 167 patients with VSA diagnosed by spasm provocation tests (SPTs) using acetylcholine, which recorded the frequencies of positive reactions to a low dose of acetylcholine (L-ACh), total occlusion due to spasm (TOC), focal spasm, and the unavoidable use of nitroglycerin (unavoidable-NTG) during SPTs. The patients underwent a medical interview that investigated the maximum duration and frequency of chest symptoms as well as the frequencies of variant angina and other serious symptoms. The patients were divided into two groups based on the maximal duration: The short-duration group (< 15 min; n = 114) and the long-duration group (≥ 15 min; n = 53). They were also divided into two groups based on the frequency of chest symptoms: The low-frequency group (< 4/mo; n = 88) and the high-frequency group (≥ 4/mo; n = 79). RESULTS The long-duration group showed higher frequencies of other serious symptoms ( P < 0.001) and variant angina ( P < 0.05) as well as higher frequencies of spasm induction by L-ACh ( P < 0.05), TOC ( P < 0.05), focal spasm ( P < 0.01), and unavoidable-NTG ( P < 0.01) than the short-duration group. These parameters did not differ significantly between the low-frequency and high-frequency groups. CONCLUSION These findings suggest that patients with VSA who experience prolonged chest symptoms may have more severe characteristics of VSA.

Background: Despite significant interest in intracoronary thrombi in patients with vasospastic angina (VSA), the phenomenon remains unclarified. Therefore, we investigated a possible relationship using coronary angioscopy (CAS) in VSA patients. Methods: Sixty patients with VSA, for whom we could assess the spastic segment using CAS, were retrospectively studied. An intracoronary thrombus on CAS was a white thrombus and an erosion-like red thrombus. We verified the clinical characteristics and lesional characteristics as they determined the risk of intracoronary thrombus formation. Results: There were 18 (30%) patients with intracoronary thrombi. More of the patients with intracoronary thrombi were male, current smokers and had severe concomitant symptoms; however, no statistically significant difference was observed upon logistic regression analysis. There were 18 (26%) coronary arteries with intracoronary thrombi out of 70 coronary arteries recognised in the spastic segments. Furthermore, atherosclerotic changes and segmental spasms were significant factors responsible for such lesions. Conclusion: Intracoronary thrombi occurred in 30% of VSA patients and much attention should be paid to the intracoronary thrombogenicity of VSA patients.