In vivo predictors of plaque erosion in patients with ST-segment elevation myocardial infarction: a clinical, angiographical, and intravascular optical coherence tomography study.

Aims: Plaque erosion is a significant substrate of acute coronary thrombosis. This study sought to determine in vivo predictors of plaque erosion in patients with ST-segment elevation myocardial infarction (STEMI). Methods and results: A prospective series of 822 STEMI patients underwent pre-intervention optical coherence tomography. Using established diagnostic criteria, 209 had plaque erosion (25.4%) and 564 had plaque rupture (68.6%). Plaque erosion was more frequent in women <50 years when compared with those ≥50 years of age (P = 0.009). There was a similar, but less striking, trend in men (P = 0.011). Patients with plaque erosion were more frequently current smokers but had fewer other coronary risk factors (dyslipidaemia, hypertension, chronic kidney disease, and diabetes mellitus) than those with plaque rupture. There was a preponderance of plaque erosion in the left anterior descending artery (LAD; 61.2%), whereas plaque rupture was more equally distributed in both the LAD (47.0%) and right coronary artery (43.3%). Despite the similar spatial distribution of erosions and ruptures over the lengths of the coronary arteries, plaque erosion occurred more frequently near a bifurcation (P < 0.001). In the multivariable analysis, age <50 years, current smoking, absence of other coronary risk factors, lack of multi-vessel disease, reduced lesion severity, larger vessel size, and nearby bifurcation were significantly associated with plaque erosion. Nearby bifurcation and current smoking were especially notable in men, while age <50 years was most predictive in women. Conclusions: Plaque erosion was a predictable clinical entity distinct from plaque rupture in STEMI patients, and gender-specific role of risk factors in plaque erosion should be considered.

Does spotty calcification attenuate the response of nonculprit plaque to statin therapy?: A serial optical coherence tomography study.

OBJECTIVES: The aim of this study was to determine if spotty calcification decreases the response of plaque progression to statin therapy. BACKGROUND: Previous studies showed that the presence of spotty calcification is a marker of vulnerable plaque. However, the relationship between spotty calcification and plaque progression is not clear. METHODS: Ninety-six nonculprit lipid-rich plaques in 69 patients who received serial optical coherence tomography (OCT) imaging were included. Plaques were divided into three groups: spotty calcification (n = 38), calcified (n = 12) and noncalcified (n = 46) plaques. Spotty calcification was identified by the presence of a lesion <4 mm in length with an arc of calcification <90°. Changes in plaque characteristics and fibrous cap thickness (FCT) at 6 and 12 months under statin therapy were analyzed by OCT. RESULTS: The increase of FCT was sustained from baseline to 6 and 12 months in three groups: spotty calcification (62.8 ± 20.9, 126.4 ± 84.9, and 169.2 ± 81.6 µm, respectively; P < .001), calcified (59.8 ± 17.0, 93.4 ± 51.4, and 155.2 ± 61.7 µm, respectively; P < .001) and noncalcified (60.0 ± 17.2, 125.5 ± 62.1, and 161.0 ± 80.5 µm, respectively; P < .001). Intensive statin induced a greater change in FCT at 12 months than moderate statin in the spotty calcification group (P = 0.034). The mean lipid arc decreased significantly at 12 months from baseline in the three groups (P = 0.004, P = 0.023, and P < .001, respectively). CONCLUSIONS: Statin therapy was effective for plaque stabilization in plaques with and without spotty calcification. Patients with spotty calcification benefitted more from intensive statin than from moderate statin therapy.

Effective anti-thrombotic therapy without stenting: intravascular optical coherence tomography-based management in plaque erosion (the EROSION study).

AIMS: Plaque erosion, compared with plaque rupture, has distinctly different underlying pathology and therefore may merit tailored therapy. In this study, we aimed to assess whether patients with acute coronary syndrome (ACS) caused by plaque erosion might be stabilized by anti-thrombotic therapy without stent implantation. METHODS AND RESULTS: This was a single-centre, uncontrolled, prospective, proof-of concept study. Patients with ACS including ST-segment elevation myocardial infarction were prospectively enrolled. If needed, aspiration thrombectomy was performed. Patients diagnosed with plaque erosion by optical coherence tomography (OCT) and residual diameter stenosis <70% on coronary angiogram were treated with anti-thrombotic therapy without stenting. OCT was repeated at 1 month and thrombus volume was measured. The primary endpoint was >50% reduction of thrombus volume at 1 month compared with baseline. The secondary endpoint was a composite of cardiac death, recurrent ischaemia requiring revascularization, stroke, and major bleeding. Among 405 ACS patients with analysable OCT images, plaque erosion was identified in 103 (25.4%) patients. Sixty patients enrolled and 55 patients completed the 1-month follow-up. Forty-seven patients (47/60, 78.3%; 95% confidence interval: 65.8-87.9%) met the primary endpoint, and 22 patients had no visible thrombus at 1 month. Thrombus volume decreased from 3.7 (1.3, 10.9) mm3 to 0.2 (0.0, 2.0) mm3. Minimal flow area increased from 1.7 (1.4, 2.4) mm2 to 2.1 (1.5, 3.8) mm2. One patient died of gastrointestinal bleeding, and another patient required repeat percutaneous coronary intervention. The rest of the patients remained asymptomatic. CONCLUSION: For patients with ACS caused by plaque erosion, conservative treatment with anti-thrombotic therapy without stenting may be an option.

Plaque erosion delays vascular healing after drug eluting stent implantation in patients with acute coronary syndrome: An In Vivo Optical Coherence Tomography Study.

OBJECTIVES: To compare vascular healing after drug-eluting stent (DES) implantation between plaque rupture (PR) and plaque erosion (PE). BACKGROUND: Vascular response after stent implantation in patients with PR has been extensively studied. Little is known about vascular healing after stent implantation in PE. METHODS: Sixty-five ACS patients who received optical coherence tomography (OCT) imaging of the culprit lesions both before and after stent implantation at baseline as well as at 6 months were included in this study. Patients were divided into two groups: PR (n = 19) and PE (n = 24). Prestent thrombus burden and poststent intrastent structure (ISS) volume were analyzed during the index procedure. The ratio of uncovered to total stent struts per cross-section score (RUTTS) and neointimal thickness and area were measured at follow-up. RESULTS: OCT imaging showed that compared with PR, PE showed a significantly lower prestent thrombus score (34.2 ± 19.2 vs. 68.6 ± 44.2, P = 0.009) at baseline and a smaller poststent ISS volume (0.7 ± 0.9 mm3 vs. 2.1 ± 1.9 mm3 , P = 0.019). At the 6-month follow-up, PE showed a higher incidence of RUTTS >0.3 (12.2 ± 14.4 vs. 2.0 ± 4.5%, P = 0.003), thinner neointimal thickness (0.05 ± 0.02 mm vs. 0.12 ± 0.08 mm, P = 0.002), and smaller neointimal area (0.5 ± 0.2 vs. 1.2 ± 0.9 mm2 , P = 0.004) compared with PR. In a multivariate logistic model, PE was identified as an independent predictor for RUTTS >0.3. CONCLUSIONS: PE was associated with less favorable healing following DES implantation when compared to PR at 6 months, indicating longer dual-antiplatelet therapy may be necessary for patients with PE. © 2017 Wiley Periodicals, Inc.

Chronic total occlusion is associated with a higher incidence of malapposition and uncovered stent struts: OCT findings at 6 months following DES implantation.

OBJECTIVES: To compare stent coverage and malapposition in patients with chronic total occlusion (CTO) lesions and non-CTO lesions (including lipid-rich plaque [LRP] and non-lipid-rich plaque [non-LRP]) after drug-eluting stent (DES) implantation by optical coherence tomography (OCT). BACKGROUND: Different initial lesion characteristics may be related to heterogeneous vessel responses after DES implantation. However, the vessel response in patients with CTO and non-CTO lesions after stenting is unclear. Methods We retrospectively enrolled 64 patients with 68 target lesions. All of the patients underwent OCT imaging immediate after stenting and 6 months after stenting. LRP was defined as the plaque with lipid content in ≥2 quadrants. Non-LRP consisted of fibrous, fibrocalcific plaque, and lipid plaque with less than 2 quadrants lipid content. RESULTS: The malapposition (3.0%, 2.6% vs. 0.6%, P = 0.022), tissue protrusion (15.0% vs. 11.0% vs. 6.4%, P < 0.001), and intrastent thrombus (3.8% vs. 2.4% vs. 1.1%, P = 0.012) were more frequent in the CTO and LRP groups. At 6-month follow-up, malapposition (5.0% vs. 1.0% and 0.4%, P = 0.002) and cross sections with uncovered struts (23.4% vs. 8.2% and 6.6%, P < 0.001) were most frequently observed in the CTO group. Although the incidence of stent thrombosis was non-significantly higher in the CTO group than the other two groups, no events were observed in patients with CTO. CONCLUSIONS: Patients with CTO lesions showed unfavorable responses to DES in the acute phase as well as at the 6-month follow-up, indicating the important pathological link between the original lesion morphology underneath the stents and heterogeneous artery healing. © 2017 Wiley Periodicals, Inc.

Incidence and Clinical Significance of Poststent Optical Coherence Tomography Findings: One-Year Follow-Up Study From a Multicenter Registry.

BACKGROUND: Optical coherence tomography (OCT) was recently introduced to optimize percutaneous coronary intervention. However, the exact incidence and significance of poststent OCT findings are unknown. METHODS AND RESULTS: A total of 900 lesions treated with 1001 stents in 786 patients who had postprocedure OCT imaging were analyzed to evaluate the incidence of poststent OCT findings and to identify the OCT predictors for device-oriented clinical end points, including cardiac death, target vessel-related myocardial infarction, target lesion revascularization, and stent thrombosis. Patients were followed up to 1 year. Stent edge dissection was detected in 28.7% of lesions, and incomplete stent apposition was detected in 39.1% of lesions. The incidences of smooth protrusion, disrupted fibrous tissue protrusion, and irregular protrusion were 92.9%, 61.0%, and 53.8%, respectively. Small minimal stent area, defined as a lesion with minimal stent area <5.0 mm(2) in a drug-eluting stent or <5.6 mm(2) in a bare metal stent, was observed in 40.4% of lesions. One-year device-oriented clinical end points occurred in 33 patients (4.5%). Following adjustment, irregular protrusion and small minimal stent area were independent OCT predictors of 1-year device-oriented clinical end points (P=0.003 and P=0.012, respectively). CONCLUSIONS: Abnormal poststent OCT findings were frequent. Irregular protrusion and small minimal stent area were independent predictors of 1-year device-oriented clinical end points, which were primarily driven by target lesion revascularization.

Pancoronary plaque vulnerability in patients with acute coronary syndrome and ruptured culprit plaque: a 3-vessel optical coherence tomography study.

BACKGROUND: Recent studies described different clinical and underlying plaque characteristics between patients with and without plaque rupture presenting with acute coronary syndrome (ACS). In light of the systemic nature of atherosclerosis, we hypothesized that nonculprit plaques might also express different morphological features in these 2 groups of patients. METHODS: Thirty-eight patients with ACS who underwent 3-vessel optical coherence tomography imaging were identified from the Massachusetts General Hospital Optical Coherence Tomography Registry. Based on culprit plaque morphology, the study population was divided into 2 groups: patients with plaque rupture at the culprit lesion (group 1) and patients with nonruptured plaque at the culprit lesion (group 2). Prevalence and features of nonculprit plaques were compared between the 2 groups. RESULTS: A total of 118 nonculprit plaques were analyzed. Patients in group 1 (n = 17) had nonculprit plaques with higher prevalence of thin-cap fibroatheroma (52.9% vs 19.0%, P = .029) and disruption (35.3% vs 4.8%, P = .016) compared with patients in group 2 (n = 21). Nonculprit plaques in group 1 showed wider maximum lipid arc (198.9° ± 41.7° vs 170.2° ± 41.9°, P = .003), greater lipid length (7.8 ± 4.4 mm vs 5.1 ± 2.4 mm, P = .003), higher lipid index (1196.9 ± 700.5 vs 747.7 ± 377.3, P = .001), and thinner fibrous cap (107.0 ± 56.5 µm vs 137.3 ± 69.8 µm, P = .035) compared with those in group 2. CONCLUSIONS: The present study showed distinctive features of nonculprit plaques between patients with ACS caused by plaque rupture and patients with ACS caused by nonruptured plaques. Patients with plaque rupture had increased pancoronary vulnerability in nonculprit plaques, suggesting that a more aggressive treatment paradigm aiming at the stabilization of vulnerable plaques may offer additional benefit to these patients.

Validation of a new animal model of vulnerable plaques by intravascular optical coherence tomography in vivo.

We aimed to establish a rabbit model of vulnerable plaques (VPs) with the morphology and component characteristics of human VPs and to evaluate the microstructural features of VPs in vivo using intravascular optical coherence tomography (OCT). Twelve rabbits underwent endothelial denudation of the carotid artery and consumed a 1% high-cholesterol diet (HCD). They were equally divided into two groups: group A (modified needle injury) and group B (balloon injury). OCT was undertaken thrice before injury as well as 1 h and 12 weeks after injury. The degree of acute artery injury after endothelial denudation was detected by OCT. Twelve weeks after injury, OCT showed that both groups generated VPs which had thin fibrous caps and a large lipid core, whereas plaques in group A had smaller lipid arcs (P < 0.0001). Histological findings demonstrated that a larger eccentricity index (EI) (P < 0.05) and greater infiltration of macrophages (P < 0.05) in group A than in group B. Qualitative and morphometric analyses of plaques showed a significant correlation between histological and OCT measurements. A combination of modified endothelial denudation and an HCD in rabbits produced more eccentric lesions similar to those seen in humans. These data suggest that OCT could be a useful tool for evaluation of the degree of injury and VPs in vivo.

[Progress on nitrogen regulation gene expression of plant pathogenic fungi under nitrogen starvation].

It has been confirmed that the occurrence of plant disease is caused by the effector molecules secreted by plant pathogens. The regulation effector gene expression is an important aspect in understanding of the infection process. The nutritional status of cells has been postulated to be a vital role for effector gene expression. Studies have indicated that the induction of the same effecter genes during growth in vitro as those during growth in planta under nitrogen-starved conditions. This showed that the nitrogen poor environment existed in the early time of plant evolution. This paper describes the system in the pathogenesis of several fungal pathogens and nitrogen in the process of gene expression effects from the results of several species by comparing and contrasting the function of nitrogen regulatory genes, as well as by studying plants in vivo and in vitro gene under nitrogen limitation inductive effect in order to reveal the effectiveness of nitrogen in the development process of host plant disease is an important factor.

Attenuation of CHOP-mediated myocardial apoptosis in pressure-overloaded dominant negative p38α mitogen-activated protein kinase mice.

BACKGROUND/AIMS: Pressure overload stimulation is known to elicit disturbances in the endoplasmic reticulum (ER), which leads to ER stress (ERS). p38 mitogen-activated protein kinase (MAPK) plays an important role in mediating apoptotic processes, however, the roles of this kinase in activating ERS-initiated apoptosis in pressure-overloaded hearts are largely unknown. METHODS: We clarified the role of p38α MAPK in ERS-associated apoptosis by subjecting transgenic mice displaying cardiac specific dominant negative (DN) mutant p38α MAPK over-expression to seven day pressure overload. RESULTS: Seven days pressure overload resulted in the same extent of cardiac hypertrophy and ERS in the wild-type (WT) and DN p38α mice compared with the sham mice. It also activated inositol-requiring enzyme (Ire)-1α and its downstream molecule, tumor necrosis factor receptor (TNFR)-associated factor (TRAF)2 in the WT and DN p38α mice compared with the sham mice. Interestingly, increased myocardial apoptosis and the up-regulation of CCAAT/enhancer binding protein homology protein (CHOP) expression compared with those in the sham mice were found in the aortic-banded WT mice, but not in the DN p38α mice. CONCLUSION: Partial inhibition of p38α protein blocked the activation of CHOP-mediated apoptotic processes during pressure overload by partially inhibiting signaling from the Ire-1α/TRAF2 to its down-stream molecule, CHOP.

[Genome-wide analysis of the secreted proteins of phytophthora infestans].

Based on the Phytophthora infestans genome sequence, we used bioinformatics and computer-based prediction algorithms to predict the secreted proteins of P infestans in detail, which would help us to elucidate the molecular mechanism underlying the interaction between the host plants and the P infestans. In this study, the signal peptide prediction algorithms SignalP v3.0 and PSORT, transmembrane helix prediction algorithms TMHMM-2.0 and THUMBUP, GPI-anchoring site prediction algorithm big-PI Predictor, and subcellular protein location distribution algorithm TargetP v1.01 were used to analyze the 22658 protein sequences of P infestans published. Our results suggested that there might be 671 secreted pro- teins, accounting for 3.0% of the total proteins. Among them, the functions of the 45 secreted proteins had been described previously. Their functions involved cellular metabolism and signal transduction etc. In addition, some of the secreted proteins were functionally similar to elicitin, which were likely to be associated with the virulence of P. infestans.

Partial inactivation of cardiac 14-3-3 protein in vivo elicits endoplasmic reticulum stress (ERS) and activates ERS-initiated apoptosis in ERS-induced mice.

BACKGROUND/AIMS: Excessive endoplasmic reticulum stress (ERS) triggers apoptosis in various conditions including diabetic cardiomyopathy and pressure overload-induced cardiac hypertrophy and heart failure. The primary function of 14-3-3 protein is to inhibit apoptosis, but the roles of this protein in protecting against cardiac ERS and apoptosis are largely unknown. METHODS: We investigated the roles of 14-3-3 protein in vivo during cardiac ERS and apoptosis induced by pressure overload or thapsigargin injection using transgenic (TG) mice that showed cardiac-specific expression of dominant negative (DN) 14-3-3eta. RESULTS: Cardiac positive apoptotic cells and the expression of glucose-regulated protein (GRP)78, inositol-requiring enzyme (Ire)1alpha, tumor necrosis factor receptor (TNFR)-associated factor (TRAF)2, CCAAT/enhancer binding protein homology protein (CHOP), caspase-12, and cleaved caspase-12 protein were significantly increased in the pressure-overload induced DN 14-3-3eta mice compared with that in the WT mice. Furthermore, thapsigargin injection significantly increased the expression of GRP78 and TRAF2 expression in DN 14-3-3eta mice compared with that in the WT mice. CONCLUSION: The enhancement of 14-3-3 protein may provide a novel protective therapy against cardiac ERS and ERS-initiated apoptosis, at least in part, through the regulation of CHOP and caspase-12 via the Ire1alpha/TRAF2 pathway.

14-3-3 protein protects against cardiac endoplasmic reticulum stress (ERS) and ERS-initiated apoptosis in experimental diabetes.

Diabetic cardiomyopathy and nephropathy induce endoplasmic reticulum stress (ERS) and ERS-initiated apoptosis. The primary function of 14-3-3 protein is to inhibit apoptosis, but the roles of this protein in protecting against cardiac ERS and apoptosis in the diabetic heart are largely unknown. In this study, we investigated the in vivo role of 14-3-3 protein in diabetic ERS and apoptosis using streptozotocin (STZ)-induced transgenic mice that showed cardiac-specific expression of a dominant negative (DN) 14-3-3eta protein mutant. The expression levels of cardiac glucose-regulated protein (GRP) 78, inositol-requiring enzyme (Ire) 1alpha, and tumor necrosis factor receptor (TNFR)-associated factor (TRAF) 2 protein were significantly increased in the diabetic DN 14-3-3eta mice compared with the diabetic wild-type. Moreover, cardiac apoptosis and the expression of CCAAT/enhancer binding protein homology protein (CHOP), caspase-12, and cleaved caspase-12 protein were significantly increased in the diabetic DN 14-3-3eta mice. In conclusion, partial depletion of 14-3-3 protein in the diabetic heart exacerbates cardiac ERS and activates ERS-induced apoptosis pathways, at least in part, through the regulation of CHOP and caspase-12 via the Ire1alpha/TRAF2 pathway. The enhancement of 14-3-3 protein expression can be used as a novel protective therapy against ERS and ERS-initiated apoptosis in the diabetic heart.

Frequency, Predictors, Distribution, and Morphological Characteristics of Layered Culprit and Nonculprit Plaques of Patients With Acute Myocardial Infarction: In Vivo 3-Vessel Optical Coherence Tomography Study.

BACKGROUND: Subclinical atherothrombosis and plaque healing may lead to rapid plaque progression. The histopathologic healed plaque has a layered appearance when imaged using optical coherence tomography. We assessed the frequency, predictors, distribution, and morphological characteristics of optical coherence tomography layered culprit and nonculprit plaques in patients with acute myocardial infarction. METHODS: A prospective series of 325 patients with acute myocardial infarction underwent optical coherence tomography imaging of all 3 native coronary arteries. Layered plaque phenotype had heterogeneous signal-rich layered tissue located close to the luminal surface that was clearly demarcated from the underlying plaque. RESULTS: Layered plaques were detected in 74.5% of patients with acute myocardial infarction. Patients with layered culprit plaques had more layered nonculprit plaques; and they more often had preinfarction angina, ST-segment-elevation myocardial infarction, higher low-density lipoprotein cholesterol, and absence of antiplatelet therapy. Layered plaques tended to cluster in the proximal segment of the left anterior descending artery and left circumflex artery but were more uniformly distributed in the right coronary artery. As compared with nonlayered plaques, layered plaques had greater optical coherence tomography lumen area stenosis at both culprit and nonculprit sites. The frequency of layered plaque phenotype (P=0.038) and maximum area of layered tissue (P<0.001) increased from nonculprit thin-cap fibroatheromas to nonculprit ruptures to culprit ruptures. CONCLUSIONS: Layered plaques were identified in 3-quarters of patients with acute myocardial infarction, especially in the culprit plaques of patients with ST-segment-elevation myocardial infarction. Layered plaques had a limited, focal distribution in the left anterior descending artery, and left circumflex artery but were more evenly distributed in the right coronary artery and were characterized by greater lumen narrowing at both culprit and nonculprit sites. Graphic Abstract: A graphic abstract is available for this article.

Dominant-negative p38alpha mitogen-activated protein kinase prevents cardiac apoptosis and remodeling after streptozotocin-induced diabetes mellitus.

The p38 mitogen-activated protein kinase (MAPK) is activated during heart diseases that might be associated with myocardial damage and cardiac remodeling process. Diabetic cardiomyopathy is associated with increased oxidative stress and inflammation. The purpose of this study was to investigate the role of p38alpha MAPK after experimental diabetes by using transgenic (TG) mice with cardiac-specific expression of a dominant-negative mutant form of p38alpha MAPK. The elevation of blood glucose was comparable between the nontransgenic (NTG) and TG mice. The expression of phospho-p38 MAPK and phospho-MAPK-activated protein kinase 2 levels were significantly suppressed in TG mice heart than in NTG mice after diabetes induction. Left ventricular (LV) dimension in systole was smaller, and the percent fractional shortening was higher in diabetic TG mice compared with diabetic NTG mice. In addition, diabetic TG mice had reduced cardiac myocyte diameter, content of cardiac fibrosis, LV tissue expressions of atrial natriuretic peptide, transforming growth factor beta1, and collagen III compared with diabetic NTG mice. Moreover, LV expression of NADPH oxidase subunits, p22(phox), p67(phox), gp91(phox), and Nox4, reactive oxygen species and lipid peroxidation levels were significantly increased in diabetic NTG mice, but not in diabetic TG mice. Furthermore, myocardial apoptosis, the number of caspase-3-positive cells, and the downregulation of antiapoptotic protein Bcl-X(L) were less in diabetic TG mice compared with diabetic NTG mice. In conclusion, our data establish that p38alpha MAPK activity is required for cardiac remodeling after diabetes induction and suggest that p38alpha MAPK may promote cardiomyocyte apoptosis by downregulation of Bcl-X(L).

Characteristics and significance of healed plaques in patients with acute coronary syndrome and stable angina: an in vivo OCT and IVUS study.

AIMS: The aim of this study was to determine the prevalence and significance of plaque with a multilayered (ML) pattern in patients with acute coronary syndrome (ACS) versus stable angina pectoris (SAP) using OCT. METHODS AND RESULTS: Two hundred and four patients (144 ACS and 60 SAP) with OCT imaging of the culprit lesions before intervention were studied. ML plaques were identified by OCT as plaque with multiple layers of distinct optical signals. ML plaque was identified in 119 out of 204 (58.3%) patients. ML plaques were more frequently observed in SAP than ACS (75% vs 51.4%, p=0.001). Patients with prior myocardial infarction (MI) had a higher incidence of ML plaque compared with those without (74.4% vs 54.5%, p=0.024). ML plaque had a higher degree of luminal stenosis (p=0.006), longer lesion length (p=0.025), more complex lesion type (B2/C) (p<0.001) on angiography and non-significant larger plaque burden (p=0.07) on IVUS compared with those without an ML pattern. CONCLUSIONS: ML plaques, indicative of prior thrombosis, were frequently identified in patients with CAD, particularly more so in SAP and those with prior MI compared with ACS. The presence of an ML pattern is a marker of a greater extent and severity of CAD, suggesting a pathogenic link between plaque healing and lesion progression.

Pre-infarction angina and culprit lesion morphologies in patients with a first ST-segment elevation acute myocardial infarction: insights from in vivo optical coherence tomography.

AIMS: This study aimed to evaluate the relationship between pre-infarction angina (PIA) and in vivo culprit lesion characteristics as assessed by intravascular optical coherence tomography (OCT) in patients with a first ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: A total of 305 consecutive patients with a first STEMI who underwent OCT imaging of culprit lesions during primary percutaneous coronary intervention (PCI) were prospectively enrolled. OCT findings of the culprit plaque were compared between patients with (n=206) and without PIA (n=99). Patients with PIA showed lower rates of thin-cap fibroatheroma (TCFA) (62.6% vs. 80.8%, p=0.001) and plaque rupture (56.8% vs. 72.7%, p=0.007), smaller maximum ruptured cavity areas (1.10±1.04 mm2 vs. 1.53±1.20 mm2, p=0.002), and more severe residual luminal narrowing (p=0.015) with a higher incidence of white residual thrombus (68.4% vs. 50.0%, p=0.003) at the culprit lesions than patients without PIA. No significant differences in clinical outcomes were observed at the one-year follow-up. CONCLUSIONS: In patients with a first STEMI, PIA was significantly associated with a lower incidence of TCFA and plaque rupture, a smaller ruptured cavity area, more white residual thrombi, and more severe lumen stenosis at the culprit lesions.

A fragment of the Xanthomonas oryzae pv. oryzicola harpin HpaG Xooc reduces disease and increases yield of rice in extensive grower plantings.

Harpins of phytopathogenic bacteria stimulate defense and plant growth in many types of plants, conferring disease resistance and enhanced yield. In a previous study, we characterized nine fragments of the harpin protein HpaG(Xooc) from Xanthomonas oryzae pv. oryzicola for plant defense elicitation and plant growth stimulation activity relative to the intact protein. In plants grown under controlled conditions, the fragment HpaG10-42 was more active in both regards than HpaG(Xooc). Here, we demonstrate that the activity of HpaG10-42 in rice under field conditions significantly exceeds that of HpaG(Xooc), stimulating resistance to three important diseases and increasing grain yield. We carried out tests in 672 experimental plots with nine cultivars of rice planted at three locations. Application protocols were optimized by testing variations in application rate, frequency, and timing with respect to rice growth stage. Of the concentrations (24, 24, 12, and 6 microg/ml), and number and timing of applications (at one to four different stages of growth) tested, HpaG10-42 at 6 microg/ml applied to plants once at nursery seedling stage and three times in the field was most effective. Bacterial blight, rice blast, and sheath blight were reduced 61.6 and 56.4, 93.6 and 76.0, and 93.2 and 55.0% in indica and japonica cultivars, respectively, relative to controls. Grain yields were 22 to 27% greater. These results are similar to results obtained with typical local management practices, including use of chemicals, to decrease disease severities and increase yield in rice. Our results demonstrate that the HpaG10-42 protein fragment can be used effectively to control diseases and increase yield of this staple food crop.

The role of the Grb2-p38 MAPK signaling pathway in cardiac hypertrophy and fibrosis.

Cardiac hypertrophy is a common response to pressure overload and is associated with increased mortality. Mechanical stress in the heart can result in the integrin-mediated activation of focal adhesion kinase and the subsequent recruitment of the Grb2 adapter molecule. Grb2, in turn, can activate MAPK cascades via an interaction with the Ras guanine nucleotide exchange factor SOS and with other signaling intermediates. We analyzed the role of the Grb2 adapter protein and p38 MAPK in cardiac hypertrophy. Mice with haploinsufficiency of the Grb2 gene (Grb2(+/-) mice) appear normal at birth but have defective T cell signaling. In response to pressure overload, cardiac p38 MAPK and JNK activation was inhibited and cardiac hypertrophy and fibrosis was blocked in Grb2(+/-) mice. Next, transgenic mice with cardiac-specific expression of dominant negative forms of p38alpha (DN-p38alpha) and p38beta (DN-p38beta) MAPK were examined. DN-p38alpha and DN-p38beta mice developed cardiac hypertrophy but were resistant to cardiac fibrosis in response to pressure overload. These results establish that Grb2 action is essential for cardiac hypertrophy and fibrosis in response to pressure overload, and that different signaling pathways downstream of Grb2 regulate fibrosis, fetal gene induction, and cardiomyocyte growth.

Is age an important factor for vascular response to statin therapy? A serial optical coherence tomography and intravascular ultrasound study.

OBJECTIVE: Age-related structural and functional changes in vessel wall may affect the time course of vascular response to statin therapy. In this study, we sought to compare the response of lipid-rich plaque to statin therapy in elderly versus younger patients using optical coherence tomography and intravascular ultrasound. PATIENTS AND METHODS: Sixty-nine patients who underwent serial optical coherence tomography and intravascular ultrasound at the time point of baseline, 6, and 12 months were divided into two groups according to median age: group A (age<57 years, n=35) and group B (age≥57 years, n=34). Patients were treated with intensive (atorvastatin 60 mg/day) or moderate (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) statin therapy. RESULTS: A continuous increase in fibrous-cap thickness (FCT) from baseline to 12 months was observed in both groups (P<0.001, <0.001, respectively). Intensive statin induced greater percent change in FCT at 12 months than moderate statin in group B (P=0.020), but not in group A (P=0.251). Mean lipid arc decreased significantly at 12 months in two groups (P<0.001, <0.001, respectively), and this response was delayed for 6 months (P=0.403) and began to decrease during the second 6 months (P<0.001) in group B. Normalized total atheroma volume decreased significantly in group A (P<0.001), but not in group B (P=0.349). CONCLUSION: Statin therapy could stabilize lipid-rich plaque irrespective of age, and intensive statin therapy was more effective than a moderate dose of statin in increasing FCT, particularly in older patients. A delayed response of lipid content and unfavorable change in normalized total atheroma volume to statin were observed in elderly patients.