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Turpeinen H Raitoharju E Oksanen A Oksala N Levula M Lyytikäinen LP Järvinen O Creemers JW Kähönen M Laaksonen R Pelto-Huikko M Lehtimäki T Pesu M 《Atherosclerosis》2011,219(2):799-806
Background
Proprotein convertase subtilisin/kexin (PCSK) enzymes cleave proproteins into mature end products. Previously, MBTPS1 and PCSK9 have been shown to regulate cholesterol metabolism and LDL receptor recycling, whereas FURIN and PCSK5 have been suggested to inactivate lipases and regulate inflammation in atherosclerosis. Here, we systematically analyzed the expression of PCSKs and their targets in advanced atherosclerotic plaques.Methods and results
Microarray and quantitative real-time PCR experiments showed that FURIN (42.86 median fold, p = 2.1e−8), but no other PCSK, is universally overexpressed in the plaques of different vascular regions. The mRNA expression screen of PCSK target proteins in plaques identified many known factors, but it also identified the significant upregulation of the previously overlooked furin-processed B cell activating cytokines APRIL (TNFSF13, 2.52 median fold, p = 3.0e−5) and BAFF (TNFSF13B, 2.97 median fold, p = 7.6e−6). The dysregulation of FURIN did not associate with its htSNPs or the previously reported regulatory SNP (−229, rs4932178) in the promoter. Immunohistochemistry experiments showed the upregulation of FURIN in the plaque lymphocytes and macrophages where it was co-expressed with BAFF/TNFSF13B and APRIL/TNFSF13.Conclusions
Our data unequivocally show that FURIN is the primary PCSK that is dysregulated in the immune cells of advanced human atherosclerotic plaques, which implies a role for this enzyme in plaque pathology. Therefore, drugs that inhibit FURIN in arteries may modulate the course of this disease. 相似文献5.
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Umberto Benedetto Massimo Caputo Mario Gaudino Roberto Marsico Cha Rajakaruna Alan Bryan Gianni D. Angelini 《The Journal of thoracic and cardiovascular surgery》2017,153(1):79-88.e4
Objectives
We conducted propensity score matching to determine whether the use of the right internal thoracic artery (RITA) confers a survival advantage when compared with the radial artery (RA) as second arterial conduit in coronary artery bypass grafting.Methods
The study population included a highly selected low-risk group of patients who received the RITA (n = 764) or the RA (n = 1990) as second arterial conduit. We obtained 764 matched pairs that were comparable for all pretreatment variables. A time-segmented Cox regression model that stratified on the matched pairs was used to investigate the effect of treatment on late mortality.Results
After a mean follow-up of 10.2 ± 4.5 years (maximum 17.3 years), survival probabilities at 5, 10, and 15 years were 96.4% ± 0.7% versus 95.4% ± 0.7%, 91.0% ± 1.1% versus 89.1% ± 1.2%, and 82.4% ± 1.9% versus 77.2% ± 2.5% in the RITA and RA groups, respectively. During the first 4 years, RITA and RA were comparable in terms of mortality (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.56-1.78; P = .98). However, after 4 years RITA was associated with a significant reduction in late mortality (HR, 0.67; 95% CI, 0.48-0.95; P = .02). RITA was superior to RA when the experimental conduit was used to graft the left coronary system (HR, 0.69; 95% CI, 0.47-0.99; P = .04) but not the right coronary system (HR, 0.98; 95% CI, 0.59-1.62; P = .93).Conclusions
In a highly selected low-risk group of patients, the use of the RITA as second arterial conduit instead of the RA was associated with better survival when used to graft the left but not the right coronary artery. 相似文献7.
Laura L. Hocum Stone Cory Swingen Christopher Holley Christin Wright Erin Chappuis Herbert B. Ward Edward O. McFalls Rosemary F. Kelly 《The Journal of thoracic and cardiovascular surgery》2017,153(3):582-590
Objective
Clinical studies demonstrate delayed recovery of hibernating myocardium (HM) following coronary artery bypass graft (CABG) surgery. Cardiac magnetic resonance (CMR) imaging is effective in identifying HM in clinical settings. Our animal model of HM shows partial but incomplete functional recovery 1 month following CABG using echocardiography. This study uses CMR imaging to determine completeness of recovery 3 months post-CABG.Methods
Swine (N = 12) underwent left anterior descending artery (LAD) 1.5-cm constrictor placement creating a territory of HM over 12 weeks. CMR at 12 weeks confirmed hibernation without infarction (N = 12). Off-pump left internal thoracic artery (LITA) to the LAD was performed in 9 animals. Three animals were killed as HM controls. CMR imaging was repeated in revascularized animals before death at 1 (n = 4) or 3 months (n = 5). CMR imaging was performed at baseline and with dobutamine infusion (5 μg/kg/min).Results
Twelve weeks after constrictor placement, CMR imaging confirmed viability in LAD region and LAD stenosis in all animals. In HM, wall thickening is reduced at baseline but with contractile reserve present during dobutamine infusion. Following revascularization, CMR imaging confirmed patent LITA graft (n = 9). Analysis of baseline regional function shows incomplete recovery of HM following CABG, with reduced contractile reserve at both 1 and 3 months post-CABG.Conclusions
CMR imaging provides accurate spatial resolution of regional contractile function and confirms the presence of HM at 12 weeks following instrumentation of the LAD. Three months following CABG, partial recovery of HM with contractile reserve is present in the single LAD territory. 相似文献8.
Lorenzo Di Bacco Alberto Repossini Maurizio Tespili Claudio Muneretto Gianluigi Bisleri 《Cardiovascular Revascularization Medicine》2019,20(1):22-28
Purpose
To evaluate the impact of the revascularization technique (by means of conventional, total arterial or hybrid myocardial revascularization) in patients with multivessel coronary artery disease.Methods
A propensity-score analysis of patients undergoing myocardial revascularization from 1998 to 2012 was performed based on the surgical technique utilized, either total arterial (Group1, G1,n°?=?89), conventional CABG(LIMA on LAD plus veins, Group2, G2,n°?=?89), or hybrid revascularization (LIMA on LAD plus PTCA on non-LAD vessels, Group3, G3, n°?=?89). Primary end-points were overall survival and cardiac-related death while secondary composite end-point was survival freedom from major adverse cardiac and cerebrovascular events (MACCEs) defined as myocardial infarction, cardiac death, stroke and repeated target vessel revascularization.Results
Study population was mostly affected by double-vessels disease (G1?=?2.35 vs G2?=?2.3 vs G3?=?2.4, p?=?0.14) with a preserved LV function(G1?=?48% vs G2?=?49% vs G3?=?50%, p?=?0.12). Hospital mortality was 0% in all groups. At a mean follow-up of 6?±?2?years overall survival was significantly better in patients receiving total arterial myocardial revascularization (G1?=?90.4?±?3.5% vs G2?=?82.3?±?4.2% vs G3?=?82.1?±?5.9%, p?=?0.049) as well as freedom from MACCEs (G1?=?95.2?±?2.4% vs G2?=?86.5?±?4% vs G3?=?68?±?6.9%, p?=?0.001) while survival free from cardiac-related death was similar(G1?=?97.7?±?1.6% vs G2?=?95.1?±?2.4% vs G3?=?89.5?±?5.4%, p?=?0.08). Conversely, at 10?years follow-up only freedom from MACCEs was significantly better in patients of Group 1(G1?=?78.9?±?8.6% vs G2?=?72.4?±?5.7% vs G3?=?52?±?8.7%, p?<?0.001).Conclusions
Total arterial revascularization provides improved outcomes at mid and long term follow-up compared with conventional or hybrid revascularization. The latter technique is particularly associated with a significantly higher incidence of late myocardial infarction and repeat revascularization. 相似文献9.