Background-Understanding the precise molecular mechanisms underlying the phenomenon of restenosis after PTCA may help us to develop a new strategy for the treatment of restenosis after PTCA. The purpose of this study was to identify the genes involved in vascular restenosis. Methods and Results-Applying a differential hybridization method to a model of the balloon-injured rabbit aorta, we identified 6 cDNA clones that were upregulated after injury. Northern blot showed that 5 genes, but not apolipoprotein J (apoJ)/clusterin, were constitutively expressed in noninjured aorta and upregulated after balloon injury. ApoJ mRNA was not detectable in noninjured aorta (control), began to be expressed at 6 hours after injury, showed a peak level at 24 hours (a 48-fold increase), gradually declined, and returned to the control level at 24 weeks. Western blot and immunohistochemistry demonstrated no expression of apoJ protein in noninjured aorta, an expression of apoJ at 2 days after balloon injury, and a peak level (a 55-fold increase) at 2 to 8 weeks. The expression of apoJ protein continued until 24 weeks after injury. In situ hybridization revealed that apoJ mRNA was expressed in smooth muscle cells (SMCs) of media at 2 days after injury and in SMCs of media and neointima at 2 weeks. To analyze the function of apoJ, stably transfected rabbit SMCs were created. The expression of apoJ stimulated proliferation and migration of SMCs. Conclusions-ApoJ is dramatically induced in media and neointima after vascular injury, suggesting that apoJ contributes to restenosis after angioplasty.
uick and accurate evaluation of coronary reperfusion in patients with acute myocardial infarction (AMI) is essential to determine whether thrombolysis and/or percutaneous coronary intervention (PCI) is required to achieve reperfusion. [1][2][3][4][5][6][7] Recent advancements in transthoracic Doppler echocardiography (TTDE) have enabled direct visualization and evaluation of coronary blood flow velocity, especially in the distal left anterior descending coronary artery (LAD). [8][9][10][11][12][13][14][15][16][17][18] This technique has been applied for noninvasive evaluation of Thrombolysis in Myocardial Infarction (TIMI) flow grade, which is widely used as a valuable index of coronary reperfusion. 19 Our previous study demonstrated that preserved coronary artery flow velocity as determined by TTDE enables differentiation of TIMI 3 from TIMI 0-2 in patients with anterior AMI before PCI. 20 However, the conventional TIMI classification is a semi-quantitative grading of coronary reperfusion after AMI and is thereby limited by its subjective and categorical nature. TIMI frame count by angiography is a simple, objective, reproducible and quantitative measure of coronary reperfusion 21 that allows for better prediction of clinical outcomes after AMI. 22 An intracoronary Doppler guidewire study has demonstrated that distal coronary flow velocity inversely correlates with the TIMI frame count before PCI. 23 Therefore, we hypothesized that the measurement of LAD flow velocity by TTDE would enable quantitative evaluation of the TIMI frame count by angiography in patients with anterior AMI. To test this hypothesis, we prospectively compared reperfused distal LAD flow velocity by TTDE with the TIMI frame count by angiography in patients with anterior AMI before mechanical reperfusion therapy.
Methods
Study GroupBetween August 2001 and November 2003, 56 consecutive patients at the Department of Cardiology, Kagoshima City Hospital with a first anterior AMI before mechanical reperfusion were enrolled in the study. Inclusion criteria were: (1) typical chest pain lasting >30 min and <12 h from onset; (2) ST-segment elevation >0.2 mV in precordial leads; (3) subsequent increase in serum creatine kinase ≥2-
Methods and ResultsColor and pulsed TTDE was performed to evaluate distal left anterior descending coronary artery (LAD) reperfusion in 56 consecutive patients with a first anterior AMI before coronary intervention, and these findings were compared with the corrected TIMI frame count (cTFC) by subsequent angiography. Twenty-four of the 56 patients had LAD reperfusion (TIMI 2 or 3) by angiography. Visual antegrade distal LAD flow by color TTDE was detected in 21 of these 24 patients. In the 21 patients, diastolic peak velocity of the distal LAD flow by pulsed TTDE showed a significant correlation with cTFC by angiography (r=-0.74, p<0.001). The diagnosis of high risk with angiographic cTFC >40 by distal LAD peak velocity <21 cm/s using TTDE had a sensitivity, specificity, and accuracy of 82%, 93%, and 91%, respectively. Concl...
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