Site-Specific Effects of PECAM-1 on Atherosclerosis in LDL Receptor-Deficient Mice

Objective—Atherosclerosis is a vascular disease that involves lesion formation at sites of disturbed flow under the influence of genetic and environmental factors. Endothelial expression of adhesion molecules that enable infiltration of immune cells is important for lesion development. Platelet/endothelial cell adhesion molecule-1 (PECAM-1; CD31) is an adhesion and signaling receptor expressed by many cells involved in atherosclerotic lesion development. PECAM-1 transduces signals required for proinflammatory adhesion molecule expression at atherosusceptible sites; thus, it is predicted to be proatherosclerotic. PECAM-1 also inhibits inflammatory responses, on which basis it is predicted to be atheroprotective. Methods and Results—We evaluated herein the effect of PECAM-1 deficiency on development of atherosclerosis in LDL receptor– deficient mice. We found that PECAM-1 has both proatherosclerotic and atheroprotective effects, but that the former dominate in the inner curvature of the aortic arch whereas the latter dominate in the aortic sinus, branching arteries, and descending aorta. Endothelial cell expression of PECAM-1 was sufficient for its atheroprotective effects in the aortic sinus but not in the descending aorta, where the atheroprotective effects of PECAM-1 also required its expression on bone marrow–derived cells. Conclusion—We conclude that PECAM-1 influences initiation and progression of atherosclerosis both positively and negatively, and that it does so in a site-specific manner. (Arterioscler Thromb Vasc Biol. 2008;28:1996-2002

Perivascular mast cells regulate vein graft neointimal formation and remodeling

Objective. Emerging evidence suggests an important role for mast cells in vein graft failure. This study addressed the hypothesis that perivascular mast cells regulate in situ vascular inflammatory and proliferative responses and subsequent vein graft neointimal lesion formation, using an optimized local mast cell reconstitution method. Methods and Results. Neointimal hyperplasia was induced by insertion of a vein graft into the right carotid artery in wild type and mast cell deficient KitW−sh/W−sh mice. In some experiments, mast cells were reconstituted systemically (tail vein injection of bone marrow-derived mast cells) or locally (directly into the right neck area) prior to vein grafting. Vein graft neointimal lesion formation was significantly (P < 0.05) reduced in KitW−sh/W−sh mice. Mast cell deficiency reduced the number of proliferating cells, and inhibited L-selectin, CCL2, M-CSF and MIP-3α expression in the vein grafts. Local but not systemic mast cell reconstitution restored a perivascular mast cell population that subsequently promoted neointimal formation in mast cell deficient mice. Conclusion. Our data demonstrate that perivascular mast cells play a key role in promoting neointima formation by inducing local acute inflammatory and proliferative responses. These results suggest that ex vivo intraoperative targeting of mast cells may have therapeutic potential for the prevention of pathological vein graft remodeling

サーモグラフィーによる体表面温度の測定 2.温水負荷の効果

The body surface temperature of 41 patients suffering coldness, numbness or pain in their feet was examined using thermography. Thermographic results were analyzed quantitatively by calculating a recovery ratio as: Recovery ratio =[Total counts of thermography (Pixels) over temperature (T) after cold loading] ÷ [Initial counts over T before cold loading] x 100(%). Three different baseline temperatures, 26℃. 27℃ and 28℃, were used in processing the thermographic results into pictures. The recovery ratio was susceptible to temperature, and we recommend a baseline temperature limitation of 27℃ for clinical study. A bi-modal distribution of recovery ratio was observed in 18 patients with diabetes mellitus. One group (6 subjects) had high recovery ratio between 80%-100%, and another group (10 subjects) had a low recovery ratio between 0%-19%. The results of thermography were also influenced by weather. To reduce the effect of outside temperature, we used pre-loading with hot water at 36℃ for 5 min (hot loading).　A large difference in　recovery ratio between presence and absence of hot loading was observed in 6 of the 30 subjects. The difference was over-estimated in more than 20% of recovery ratio without hot loading as compared with hot loading in these 6 subjects. The effect of drugs on peripheral circulation, such as beraprost sodium and sarpogrelate hydrochloride, was clear and quantified using thermography under these conditions of hot loading.下肢に冷感ならびにしびれ感または疼痛を訴える患者41症例についてサーモグラフィーを用いて体表面温度を測定した｡測定で得られた結果は回復率として数量化して表示された｡回復率の算出方法は回復率=[冷水負荷後の特定温度T℃以上の体表面温度のサーモグラフィーのPixelの総数]÷[温水負荷前の特定温度T℃以上の体表面温度のサーモグラフィーのPixelの総数]× 100%で求めた｡サーモグラフィーで得られた結果と画像処理の過程で用いられた,26℃,27℃,28℃の3つの異なる特定温度T℃ との関連について検討を行なった｡その結果,回復率は特定温度T℃に影響を受けやすいことが明らかとなった｡下肢の体表面温度の低い臨床症例においては27℃の条件が適当と考えられた｡前述の41症例中の18症例の糖尿病患者について検討を行なった｡そのサーモグラフィーの結果は,比較的回復率の高い(80%～100%)群の6症例と比較的回復率の低い(0%～19%)群の10症例の2群に別れた｡わずかに残り2症例が20%から79%の間であった｡下肢の症状が気温の低い時期に出親しやすいためにサーモグラフィーの検査を冬期に行なう必要性が高まった｡しかし,天候の影響を受けやすいために冷水負荷前の測定領域の下肢が冷えすぎているために20℃の室温に15分間の安静時間では体表面温度が十分に暖まることが出来ず,27℃以上の領域として測定範囲全体を観察できない 問題に直面した｡この間温点を解決する手段として36℃の温水に5分間下肢を入れて暖める温水負荷を加えることにした｡そこで, 温水負荷を行なった症例30症例について,温水負荷を行なう前(室温)の回復率と温水負荷を行なった後の回復率について比較検討を行なったところ,20%にあたる6症例において温水負荷を行なわなかった場合に20%以上の回復率の過剰評価が認めら れた｡温水負荷を行なうことにより年間を通じて天候の影響を最小限にすることが可能となり,この結果,長期間の内服薬の末梢循環に及ぼす影響の測 定を行なった場合に,季節の影響を最小限にしてサーモグラフィーにより回復率を用いて数値化された測定結果を検討することが可能となった｡具体的に末梢循環の改善に薬効が有ると言われている薬剤であるベラプロストおよびサルポグレラートを3ヵ月間内服した場合の前後のサーモグラフィーで得られた回復率について検討を行なった｡その結果はベラプロストにおいては,6.9%から41.9%に上昇または回復率の6.1倍の上昇を認めた。サルポグレラートにおいては,1.9%から17.3%に上昇または回復率の9.1倍の上昇を認めた。以上より,温水負荷を加えたサーモグラフィーの測定結果の数値化は下肢に症状の有る患者の末梢循環の評価ならびに薬効の評価の比較に有用であることが表わされた

Arterial anatomy and arteriographic diagnosis of arteriogenic impotence

One hundred twenty-six bilateral selective arteriographic examinations of the iliopudendal vascular tree were performed after comprehensive multidisciplinary evaluation in patients with chronic erectile dysfunction. Best imaging results were obtained by performing the arteriography under epidural anesthesia after intracavernous injection of a vasoactive drug combination. The arteriography is mandatory prior to revascularization procedures. It is further indicated in primary erectile dysfunction and posttraumatic erectile failure. The importance of cavernosography and selective arteriography in primary erectile dysfunction is stressed. Increasing knowledge about the influence of vasoactive drugs on penile hemodynamics has led to its application in diagnosis and therapy of erectile dysfunction. Pharmacocovernosography, Doppler-ultrasound of penile arteries after intracavernous injection of a vasoactive drug combination, and pharmacoarteriography are refined techniques to prove a vascular etiology of erectile dysfunction. The results of the morphologic studies of the vascular system are correlated with functional testing of erectile capacity by intracavernous application of a papaverinephentolamine drug combination

Reduced Necrosis and Content of Apoptotic M1 Macrophages in Advanced Atherosclerotic Plaques of Mice With Macrophage-Specific Loss of Trpc3

In previous work we reported that ApoeKO mice transplanted with bone marrow cells deficient in the Transient Receptor Potential Canonical 3 (TRPC3) channel have reduced necrosis and number of apoptotic macrophages in advanced atherosclerotic plaques. Also, in vitro studies with polarized macrophages derived from mice with macrophage-specific loss of TRPC3 showed that M1, but not M2 macrophages, deficient in Trpc3 are less susceptible to ER stress-induced apoptosis than Trpc3 expressing cells. The questions remained (a) whether the plaque phenotype in transplanted mice resulted from a genuine effect of Trpc3 on macrophages, and (b) whether the reduced necrosis and macrophage apoptosis in plaques of these mice was a manifestation of the selective effect of TRPC3 on apoptosis of M1 macrophages previously observed in vitro. Here, we addressed these questions using Ldlr knockout (Ldlr−/−) mice with macrophage-specific loss of Trpc3 (MacTrpc3−/−/Ldlr−/− → Ldlr−/−). Compared to controls, we observed decreased plaque necrosis and number of apoptotic macrophages in MacTrpc3−/−/Ldlr−/− → Ldlr−/− mice. Immunohistochemical analysis revealed a reduction in apoptotic M1, but not apoptotic M2 macrophages. These findings confirm an effect of TRPC3 on plaque necrosis and support the notion that this is likely a reflection of the reduced susceptibility of Trpc3-deficient M1 macrophages to apoptosis.Fil: Solanki, Sumeet. University of Toledo; Estados UnidosFil: Dube, Prabhatchandra R.. University of Toledo; Estados UnidosFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Vazquez, Guillermo. University of Toledo; Estados Unido

Testing Method of Stent’s Radial Force

In case of coronary arteriosclerosis and heart attack balloon-expandable stents are used. These balloon crimped implants are placed to the occluded vessel part and the balloons are pumped with big pressure (4-20 bar). The opened stents ensure the continuously flow of the blood in the opened lumen. The implants have to sustain the outer load from the vessel wall and have to keep the lumen open. In this study a method was worked out which valuating the radial force of the balloon expandable coronary stents. In an experimental program many types of methods were tested to find the best one

Antioxidant status in acute stroke patients and patients at stroke risk

Background and Purpose: Antioxidant enzymes like copper/ zinc superoxide dismutase (SOD), catalase and gluthatione peroxidase (GSHPx) are part of intracellular protection mechanisms to overcome oxidative stress and are known to be activated in vascular diseases and acute stroke. We investigated the differences of antioxidant capacity in acute stroke and stroke risk patients to elucidate whether the differences are a result of chronic low availability in arteriosclerosis and stroke risk or due to changes during acute infarction. Methods: Antioxidant enzymes were examined in 11 patients within the first hours and days after acute ischemic stroke and compared to risk- and age-matched patients with a history of stroke in the past 12 months ( n = 17). Antioxidant profile was determined by measurement of glutathione (GSH), malondialdehyde (MDA), SOD, GSHPx and minerals known to be involved in antioxidant enzyme activation like selenium, iron, copper and zinc. Results: In comparison to stroke risk patients, patients with acute ischemic stroke had significant changes of the GSH system during the first hours and days after the event: GSH was significantly elevated in the first hours (p < 0.01) and GSHPx was elevated 1 day after the acute stroke (p < 0.05). Selenium, a cofactor of GSHPx, was decreased (p < 0.01). GSHPx levels were negatively correlated with National Institutes of Health Stroke Scale (NIHSS) scores on admission (r = - 0.84, p < 0.001) and NIHSS scores after 7 days ( r = - 0.63, p < 0.05). MDA levels showed a trend for elevation in the first 6 h after the acute stroke ( p = 0.07). No significant differences of SOD, iron, copper nor zinc levels could be identified. Conclusions: Differences of antioxidant capacity were found for the GSH system with elevation of GSH and GSHPx after acute stroke, but not for other markers. The findings support the hypothesis that changes of antioxidant capacity are part of acute adaptive mechanisms during acute stroke. Copyright (C) 2004 S. Karger AG, Basel

Alzheimer and vascular brain diseases: Focal and diffuse subforms.

Alois Alzheimer is best known for his description of the pre-senile neurodegenerative disease named after him. However, his previous interest in vascular brain diseases, underlying cognitive and behavioral changes, was very strong. Besides describing the Arteriosclerotic atrophy of the brain and the arteriosclerotic subtype of Senile dementia which he viewed as main forms of vascular brain diseases, he also identified and described a series of conditions he considered subforms. These may be divided, as suggested by the authors of the present paper, into 3 groups: gliosis and sclerosis, subcortical atrophies, and apoplectic. The subforms of the three groups present characteristic neuropathological features and clinical, cognitive and behavioral manifestations. These provide the basis, together with part of the main forms, for the contemporary condition known as Vascular Cognitive Impairment