ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background—Myocardial cells from failing human hearts are characterized by abnormal calcium handling, a negative force-frequency relationship, and decreased sarcoplasmic reticulum Ca2+ATPase (SERCA2a) activity. In this study, we tested whether contractile function can be improved by decreasing the inhibitory effects of phospholamban on SERCA2a with adenoviral gene transfer of antisense phospholamban (asPL).Methods and Results—Myocardial cells isolated from 9 patients with end-stage heart failure and 18 donor nonfailing hearts were infected with adenoviruses encoding for either the antisense of phospholamban (Ad.asPL), the SERCA2a gene (Ad.SERCA2a), or the reporter genes &bgr;-galactosidase and green fluorescent protein (Ad.&bgr;gal-GFP). Adenoviral gene transfer with Ad.asPL decreased phospholamban expression over 48 hours, increasing the velocity of both contraction and relaxation. Compared with cardiomyocytes infected with Ad.asPL (n=13), human myocytes infected with Ad.&bgr;gal-GFP (n=8) had enhanced contraction velocity (20.3±3.9% versus 8.7±2.6% shortening/second;P<0.01) and relaxation velocity (26.0±6.2% versus 8.6±4.3% shortening/second;P<0.01). The improvement in contraction and relaxation velocities was comparable to cardiomyocytes infected with Ad.SERCA2a. Failing human cardiomyocytes had decreased contraction and Ca2+release with increasing frequency (0.1 to 2 Hz). Phospholamban ablation restored the frequency response in the failing cardiomyocytes to normal; increasing frequency resulted in enhanced sarcoplasmic reticulum Ca2+release and contraction.Conclusion—These results show that gene transfer of asPL can improve the contractile function in failing human myocardium. Targeting phospholamban may provide therapeutic benefits in human heart failure.

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background—In patients with Kawasaki disease, serial evaluation of the distribution and size of coronary artery aneurysms (CAA) is necessary for risk stratification and therapeutic management. Although transthoracic echocardiography is often sufficient for this purpose initially, visualization of the coronary arteries becomes progressively more difficult as children grow. We sought to prospectively compare coronary magnetic resonance angiography (MRA) and x-ray coronary angiography findings in patients with CAA caused by Kawasaki disease.Methods and Results—Six subjects (age 10 to 25 years) with known CAA from Kawasaki disease underwent coronary MRA using a free-breathing T2-prepared 3D bright blood segmented k-space gradient echo sequence with navigator gating and tracking. All patients underwent x-ray coronary angiography within a median of 75 days (range, 1 to 359 days) of coronary MRA. There was complete agreement between MRA and x-ray angiography in the detection of CAA (n=11), coronary artery stenoses (n=2), and coronary occlusions (n=2). Excellent agreement was found between the 2 techniques for detection of CAA maximal diameter (mean difference=0.4±0.6 mm) and length (mean difference=1.4±1.6 mm). The 2 methods showed very similar results for proximal coronary artery diameter (mean difference=0.2±0.5 mm) and CAA distance from the ostia (mean difference=0.1±1.5 mm).Conclusion—Free-breathing 3D coronary MRA accurately defines CAA in patients with Kawasaki disease. This technique may provide a non-invasive alternative when transthoracic echocardiography image quality is insufficient, thereby reducing the need for serial x-ray coronary angiography in this patient group.

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background—Platelet adhesion on components of the extracellular matrix and platelet activation by those components are crucial for the arrest of posttraumatic bleeding, but they can also harm tissue by occluding diseased vessels. Recent studies have shown that the activation of platelets by collagen is mediated through the same pathway used by immune receptors, with an immunoreceptor tyrosine-based activation motif on the Fc receptor &ggr; chain (FcR&ggr;) playing a pivotal role.Methods and Results—We examined the role of collagen-stimulated platelets in the development of injury-induced neointimal formation by using mice deficient in FcR&ggr;. The left femoral arteries of 8- to 12-week-old FcR&ggr;-deficient mice (n=16) and C57BL/6 (wild-type) mice (n=16) were injured by a straight spring wire (0.35-mm diameter). Segments of the injured and uninjured femoral arteries were excised at 7 days and 28 days after the vascular injury. Arterial segments were examined by immunohistochemistry and electron microscopy. Two hours after injury, electron microscopy showed marked decreases in platelet adhesion and neutrophil attachment to the vascular wall surface in FcR&ggr;-knockout mice compared with wild-type mice. At 7 days after injury, staining with anti-neutrophil antibody showed fewer neutrophils in FcR&ggr;-knockout mice than in wild-type mice. Computer-aided morphometry performed to measure the neointimal area, intima/media ratio, and stenotic area at 28 days after injury showed a significantly smaller ratio and area in FcR&ggr;-knockout mice than in wild-type mice (for neointimal area, 16 635±1406 versus 31 483±2309 &mgr;m2, respectively; for intima/media ratio, 1.25±0.40 versus 2.68±0.04, respectively; and for stenotic area, 26.8±2.1% versus 49.3±4.1%, respectively).Conclusions—These results demonstrate that FcR&ggr; may play important roles in the initiation and generation of neointimal hyperplasia after balloon injury through the activation of platelets by collagen.

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID