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Kevin Wei

Publications and source records attributed to Kevin Wei.

At least 19 recordsLinked to original sources
PubMed2026

A spatially coordinated keratinocyte-fibroblast circuit recruits MMP9+ myeloid cells to drive type I interferon-driven inflammation in photosensitive autoimmunity.

Photosensitivity is central to cutaneous lupus erythematosus and dermatomyositis (DM), but the mechanisms linking UVB exposure to tissue-specific autoimmunity are poorly defined. Using single-cell RNA sequencing, spatial transcriptomics, proteomics, UVB provocation and in vitro modeling, we identify MMP9+CD14+ myeloid cells as critical mediators of photosensitivity. These cells expand significantly in lesional skin, produce interferon-β (IFNβ) and colocalize with cytotoxic CD4+ T cells at the dermal-epidermal junction. Keratinocytes activate fibroblasts in the superficial dermis, prompting them to release chemokines (CCL2, CCL19, CCL7, CCL8) that recruit MMP9+CD14+ cells. In vitro, type I interferon-primed keratinocytes exposed to UVB release cytokines activating dendritic cells, mirroring in vivo responses. UVB irradiation of non-lesional skin of patients with DM rapidly recruits these myeloid cells. In a clinical proof-of-concept study, anti-type I interferon treatment with anifrolumab prevented UVB-induced myeloid infiltration and reduced photosensitivity. Therefore, targeting MMP9+CD14+ cells may offer therapeutic potential for managing photosensitive autoimmune skin conditions.

Humans↗
PubMed2007

Contrast echocardiography.

Myocardial contrast echocardiography (MCE) is a noninvasive imaging technique that relies on the ultrasound detection of microbubble contrast agents. These agents are confined to the intravascular space thereby producing signal enhancement from the blood pool. This review encompasses many of the key concepts regarding the clinical application of MCE. The first section focuses on the composition, safety, and biokinetics of ultrasound contrast agents. Then we discuss new ultrasound imaging methodology that has been developed to enhance detection of contrast agent and to assess perfusion at the tissue level. Next, the clinical applications of contrast ultrasound are reviewed. These include enhancement of the cardiac chambers for better assessment of cardiac function and masses, myocardial perfusion imaging for the detection of coronary artery disease, and the assessment of myocardial viability and microvascular reflow. Finally, we discuss some of the future applications for MCE, which include molecular imaging of disease and drug/gene delivery. The overall aim of the review is to update the clinician on state-of-the-art MCE and how it can be applied in patients with cardiovascular disease.

Animals↗
PubMed2006

Myocardial contrast echocardiography evolving as a clinically feasible technique for accurate, rapid, and safe assessment of myocardial perfusion: the evidence so far.

Intravenous myocardial contrast echocardiography (MCE) is a recently developed technique for assessment of myocardial perfusion. Up to now, many studies have demonstrated that the sensitivity and specificity of qualitative assessment of myocardial perfusion by MCE in patients with acute and chronic ischemic heart disease are comparable with other techniques such as cardiac scintigraphy and dobutamine stress echocardiography. Furthermore, quantitative parameters of myocardial perfusion derived from MCE correlate well with the current clinical standard for this purpose, positron emission tomography. Myocardial contrast echocardiography provides a promising and valuable tool for assessment of myocardial perfusion. Although MCE has been primarily performed for medical research, its implementation in routine clinical care is evolving. This article is intended to give an overview of the current status of MCE.

Acute Disease↗
PubMed2006

Phasic changes in arterial blood volume is influenced by collateral blood flow: implications for the quantification of coronary stenosis at rest.

BACKGROUND: The systolic to diastolic arteriolar blood volume (aBV) ratio derived using myocardial contrast echocardiography (MCE) can identify the presence of coronary stenosis at rest. There are some patients with moderate to severe coronary stenosis who nonetheless exhibit a normal systolic to disatolic aBV ratio. AIM: To test the hypothesis that collateral blood flow influences the systolic to diastolic aBV ratio. MCE-defined phasic changes in aBV were recorded at baseline and up to 2 degrees of non-critical stenosis in 12 dogs. Measurements were made from MCE-defined collateralised and non-collateralised portions of the left anterior descending arterial bed. RESULTS: Increases in both systolic and diastolic aBV were noted in the non-collateralised region with increasing degrees of stenosis. Although these increases in the absolute values did not reach statistical significance, the systolic to diastolic aBV signal ratio in the non-collateralised bed increased significantly between stages (analysis of variance, p = 0.003). In comparison, in the collateralised bed neither the absolute systolic nor diastolic aBV signals changed with increasing degrees of stenosis. Consequently, the aBV signal ratio between systole and diastole also did not change in this bed. CONCLUSION: Phasic changes in aBV are influenced by the degree of collateral blood flow. Thus, if the region of interest is not placed in the centre of the vascular bed, the degree of stenosis may be underestimated by the systolic to diastolic aBV ratio. On the other hand, as extensive collateralisation may indicate excellent prognosis, this ratio may provide prognostic information independent of the coronary anatomy.

Animals↗
PubMed2006

A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development.

The chemokine stromal cell-derived factor (SDF-1; also known as chemokine ligand 12 [CXCL12]) regulates many essential biological processes, including cardiac and neuronal development, stem cell motility, neovascularization, angiogenesis, apoptosis, and tumorigenesis. It is generally believed that SDF-1 mediates these many disparate processes via a single cell surface receptor known as chemokine receptor 4 (CXCR4). This paper characterizes an alternate receptor, CXCR7, which binds with high affinity to SDF-1 and to a second chemokine, interferon-inducible T cell alpha chemoattractant (I-TAC; also known as CXCL11). Membrane-associated CXCR7 is expressed on many tumor cell lines, on activated endothelial cells, and on fetal liver cells, but on few other cell types. Unlike many other chemokine receptors, ligand activation of CXCR7 does not cause Ca2+ mobilization or cell migration. However, expression of CXCR7 provides cells with a growth and survival advantage and increased adhesion properties. Consistent with a role for CXCR7 in cell survival and adhesion, a specific, high affinity small molecule antagonist to CXCR7 impedes in vivo tumor growth in animal models, validating this new receptor as a target for development of novel cancer therapeutics.

Animals↗
PubMed2006

VEGF modulates erythropoiesis through regulation of adult hepatic erythropoietin synthesis.

Vascular endothelial growth factor (VEGF) exerts crucial functions during pathological angiogenesis and normal physiology. We observed increased hematocrit (60-75%) after high-grade inhibition of VEGF by diverse methods, including adenoviral expression of soluble VEGF receptor (VEGFR) ectodomains, recombinant VEGF Trap protein and the VEGFR2-selective antibody DC101. Increased production of red blood cells (erythrocytosis) occurred in both mouse and primate models, and was associated with near-complete neutralization of VEGF corneal micropocket angiogenesis. High-grade inhibition of VEGF induced hepatic synthesis of erythropoietin (Epo, encoded by Epo) >40-fold through a HIF-1alpha-independent mechanism, in parallel with suppression of renal Epo mRNA. Studies using hepatocyte-specific deletion of the Vegfa gene and hepatocyte-endothelial cell cocultures indicated that blockade of VEGF induced hepatic Epo by interfering with homeostatic VEGFR2-dependent paracrine signaling involving interactions between hepatocytes and endothelial cells. These data indicate that VEGF is a previously unsuspected negative regulator of hepatic Epo synthesis and erythropoiesis and suggest that levels of Epo and erythrocytosis could represent noninvasive surrogate markers for stringent blockade of VEGF in vivo.

Animals↗
PubMed2006

Fractional flow reserve of infarct-related arteries identifies reversible defects on noninvasive myocardial perfusion imaging early after myocardial infarction.

OBJECTIVES: We hypothesized that fractional flow reserve (FFR) of an infarct-related artery (IRA) early after myocardial infarction (MI) identifies inducible ischemia on noninvasive imaging. BACKGROUND: Early after MI, IRAs frequently have angiographically indeterminant lesions. Whether FFR can detect reversible perfusion defects early after MI when dynamic microvascular abnormalities are present is not known. METHODS: Rest and dipyridamole (DP)-stress 99mTc sestamibi single-photon emission computed tomography (SPECT) were performed in 48 patients 3.7 +/- 1.3 days after MI, with 23 patients undergoing concurrent myocardial contrast echocardiography (MCE). Angiography, FFR, and percutaneous coronary intervention (PCI) of the IRA (as necessary) were subsequently performed. Follow-up SPECT was performed 11 weeks after PCI to identify true reversibility on baseline SPECT. RESULTS: The sensitivity, specificity, positive and negative predictive value, and concordance of FFR < or =0.75 for detecting reversibility on SPECT were 88%, 50%, 68%, 89%, and 71% (chi-square <0.001), respectively; which improved to 88%, 93%, 88%, 93%, and 91% (chi-square <0.001), respectively, for the detection of true reversibility. The corresponding values of FFR < or =0.75 for detecting reversibility on DP-MCE were 90%, 100%, 100%, 75%, and 93% (chi-square <0.001), respectively, and on either SPECT or MCE were 88%, 93%, 91%, 91%, and 91% (chi-square <0.001), respectively. The optimal FFR value for discriminating inducible ischemia on noninvasive imaging was 0.78. CONCLUSIONS: Fractional flow reserve of the IRA accurately identifies reversibility on noninvasive imaging early after MI. These findings support the utility of FFR early after MI.

Aged↗
PubMed2006

Effect of time delay on the diagnostic use of contrast echocardiography in patients presenting to the emergency department with chest pain and no S-T segment elevation.

BACKGROUND: The purpose of this study was to assess the effect of time delay on the diagnostic and prognostic use of contrast echocardiography (CE) in patients presenting to the emergency department (ED) with chest pain (CP) and no S-T segment elevation. METHODS: Patients (n = 957, 498 men) presenting to the ED within 12 hours of suggested cardiac CP underwent CE. Regional function (RF) and myocardial perfusion were interpreted separately by expert readers blinded to all other clinical data. Primary (acute myocardial infarction and total mortality) and secondary (unstable angina and revascularization) events within 24 hours of enrollment were determined. RESULTS: Patients were divided into 4 quartiles based on the time interval between their last episode of CP and CE. Patients in quartile I had CE during CP (time delay of 0 minutes). The time delay in quartiles II, III, and IV were 54 +/- 45, 213+/-54, and 556 +/- 184 minutes, respectively (P < .001). The incidence of events was similar among the 4 quartiles. In each quartile, patients with normal RF had the lowest incidence of events, whereas those with both abnormal RF and myocardial perfusion had the highest incidence of events. Patients with abnormal RF but normal myocardial perfusion had an intermediate event rate. CONCLUSIONS: In patients presenting to the ED within 12 hours of CP, the timing of CE does not influence its ability to predict events that occur 24 hours later. These findings have important implications in the performance of CE in the ED.

Adult↗
PubMed2005

Improvement in microvascular reflow and reduction of infarct size with adenosine in patients undergoing primary coronary stenting.

The aim of this study was to use myocardial contrast echocardiography to evaluate the effect of intravenous adenosine on microvascular reflow in patients with acute myocardial infarction who underwent primary coronary stenting (PCS). Thirty patients who underwent primary PCS for acute myocardial infarction were randomized to intravenous adenosine (50 to 70 mug/kg/min) or vehicle for 3 hours. Myocardial contrast echocardiography was performed before and sequentially after PCS to determine the risk area during coronary occlusion and infarct size. The risk area was similar in the adenosine- and placebo-treated patients. The infarct size as a ratio to the risk area was smaller in patients treated with adenosine when measured at 3 to 5 days (0.37 +/- 0.29 vs 0.68 +/- 0.25, p <0.01) and at 4 weeks (0.34 +/- 0.26 vs 0.60 +/- 0.21, p <0.01) after PCS. This effect was greatest when patency was achieved <4 hours after symptom onset (0.18 +/- 0.18 vs 0.74 +/- 0.31, p <0.05), with little effect after 4 hours. The relative microvascular blood volume in the risk area at 4 weeks was higher in patients receiving adenosine than in those receiving placebo (0.73 +/- 0.22 vs 0.57 +/- 0.20, p <0.01), and was highest when patency was achieved in <4 hours. In conclusion, the adjunctive use of intravenous adenosine after PCS reduces the infarct size relative to the risk area. This beneficial effect occurs primarily in those undergoing early intervention.

Adenosine↗
PubMed2005

Myocardial contrast echocardiography versus Thrombolysis In Myocardial Infarction score in patients presenting to the emergency department with chest pain and a nondiagnostic electrocardiogram.

OBJECTIVES: We hypothesized that regional function (RF) and myocardial perfusion (MP) are superior to the Thrombolysis In Myocardial Infarction (TIMI) score for diagnosis and prognostication in patients presenting to the emergency department (ED) with chest pain (CP) and a nondiagnostic electrocardiogram. BACKGROUND: Rapid diagnosis and prognostication is difficult in patients presenting to the ED with suspected cardiac CP. METHODS: Contrast echocardiography was performed to assess RF and MP on 957 patients presenting to the ED with suspected cardiac CP and a nondiagnostic electrocardiogram. A modified TIMI (mTIMI) score was calculated from six immediately available variables. A full TIMI score also was derived after troponin levels were able to be accessed adequately. Follow-up was performed for early (within 24 h), intermediate (30 day), and late primary (death and myocardial infarction) or secondary (unstable angina and revascularization) events. RESULTS: The mTIMI score was unable to discriminate between intermediate- compared to high-risk patients at any follow-up time point, whereas only 2 of 523 patients with normal RF had an early primary event. Regional function provided incremental prognostic value over mTIMI scores for predicting intermediate and late events. In patients with abnormal RF, MP further classified patients into intermediate- and high-risk groups. The full TIMI score could not improve upon these results at any follow-up time point. CONCLUSIONS: Contrast echocardiography can rapidly and accurately provide short-, intermediate-, and long-term prognostic information in patients presenting to the ED with suspected cardiac CP even before serum cardiac markers are known. Integrating contrast echocardiography into the ED evaluation of CP may improve the risk stratification of such patients.

Adult↗
PubMed2005

Detection of coronary stenoses at rest with myocardial contrast echocardiography.

BACKGROUND: We hypothesized that autoregulatory changes in arteriolar blood volume (aBV) that develop distal to a stenosis can be measured with myocardial contrast echocardiography, allowing coronary stenosis detection at rest without recourse to stress. METHODS AND RESULTS: Patients with varying degrees of coronary artery stenosis on quantitative angiography underwent high-mechanical-index myocardial contrast echocardiography at 15 Hz to allow measurement of phasic changes in aBV in large intramyocardial vessels using either Definity (group 1; n=22) or Imagent (group 2; n=22). Progressive increases in the BACKGROUND: <0.001) and group 2 (0.10+/-0.05, 0.27+/-0.18, 0.39+/-0.28, and 0.74+/-0.37; P<0.0001) patients. A systolic/diastolic aBV signal ratio of >0.34 provided a sensitivity and specificity of 80% and 71%, respectively, for the detection of >75% coronary stenosis in group 1 patients, whereas a ratio of >0.43 provided a sensitivity and specificity of 89% and 74%, respectively, for the detection of >75% stenosis in group 2 patients. CONCLUSIONS: Both the presence and severity of a physiologically significant coronary stenosis can be detected at rest by measuring the increase in aBV on myocardial contrast echocardiography that occurs distally to the stenosis without recourse to any form of stress.

Adult↗
PubMed2005

Regional left ventricular perfusion and function in patients presenting to the emergency department with chest pain and no ST-segment elevation.

AIMS: We hypothesized that the assessment of left ventricular regional function (RF) and myocardial perfusion (MP) will provide incremental value over routine evaluation in patients who present to the emergency department (ED) with chest pain (CP) and no ST-segment elevation. METHODS AND RESULTS: In addition to routine clinical evaluation, patients with suspected cardiac CP and no ST-segment elevation were evaluated in the ED for RF and MP using contrast echocardiography (CE). Cardiac-related death, acute myocardial infarction, unstable angina pectoris, congestive heart failure (CHF), and revascularization were considered as events within 48 h (early). Of the 1017 patients studied, 166 (16.3%) had early events. Adding RF increased the prognostic information of clinical and EKG variables significantly (Bonferroni corrected P<0.0001) for predicting these events. When MP was added, significant additional prognostic information was obtained (Bonferroni corrected P=0.0002). All patients were followed for a median of 7.7 months (25th-75th percentiles: 2.7-12.5) Of these, 292 (28.7%) had events. Adding RF increased the prognostic information of clinical and EKG variables for determining the risk of events significantly (Bonferroni corrected P<0.0001), which was further increased by adding MP (Bonferroni corrected P<0.0001). CONCLUSION: Early assessment of RF on CE adds significant diagnostic and prognostic value to routine evaluation in patients presenting to the ED with suspected cardiac CP and no ST-segment elevation. MP provides additional significant value. CE could be a valuable tool in the early triage and management of CP patients presenting to the ED.

Aged↗
PubMed2005

Assessment of myocardial viability using myocardial contrast echocardiography.

Myocardial contrast echocardiography (MCE) is a technique that uses microbubbles as a tracer during simultaneous ultrasound of the heart. The microbubbles can be used to provide quantitative information regarding the adequacy of myocardial blood flow (MBF), as well as the spatial extent of microvascular integrity. In acute myocardial infarction, MCE can identify the presence of collateral flow within the risk area, and can therefore predict preservation of myocardial viability and ultimate infarct size even prior to reperfusion. After reperfusion, the extent of microvascular no-reflow can be determined, and has significant implications for recovery of left ventricular function. In chronic ischemic heart disease, MCE has also been shown to successfully differentiate viable from necrotic myocardium. This technique can accurately predict recovery of function after revascularization. More importantly, MCE can be used to identify viable segments that may help to prevent infarct expansion and remodeling, and thus improve patient outcomes.

Animals↗
PubMed2004

The coronary microcirculation in health and disease.

Apart from being the site of nutrient and gas exchange for the myocardium, the capillary bed is a dynamic participant in the regulation of coronary and myocardial blood flow. MBV also responds to changes in myocardial oxygen demand. Because MCE can be used to assess MBF and MBV in vivo, it can be used to provide unique insights into tissue perfusion.

Blood Flow Velocity↗
PubMed2004

Myocardial contrast echocardiography in the detection of coronary stenosis.

The need for the capillary bed to maintain normal hydrostatic pressure results in capillary derecruitment distal to a stenosis during hyperemia. This pathophysiologic behavior is seen irrespective of the method by which coronary driving pressure is reduced. The functional consequences of the decrease in MBV are an increase in myocardial vascular resistance and a concomitant reduction in hyperemic MBF. These phenomena form the basis for the detection of CAD with MCE, which isa unique noninvasive tool that allows the separate assessment of both MBV and MBF velocity. Because of its excellent spatial and temporal resolution, portability, widespread availability,and relatively low cost, MCE should provide an attractive method for the noninvasive detection of CAD and for the quantification of stenosis severity.

Blood Flow Velocity↗
PubMed2004

Coxsackievirus B3 infection compromises endothelial-dependent vasodilation of coronary resistance arteries.

The mechanisms of coronary artery dysfunction in coxsackievirus B3 (CVB3)-mediated viral myocarditis are poorly understood. We used pressure myography of mouse septal coronary arteries to determine the early and late effects of CVB3 infection on vascular function. Male CD-1 mice (age 6-7 weeks) were infected with CVB3 (1.75 x 10(10) pfu, i.p.). Control mice were injected with PBS. Mice were killed at 3, 7, and 42 days post infection, and the ventricular septal artery was dissected and mounted on a pressure myograph. Pressure-induced myogenic tone was similar in CVB3-infected and sham-infected mice at 3 and 7 days post infection. However, at 42 days post infection constriction of septal arteries to pressures equal to or less than 60 mm Hg was enhanced in CVB3-infected mice compared with sham controls. Agonist-induced vasodilation, as assessed by response to acetylcholine (1 nM-3 microM), was unaltered at early time points (days 3 and 7) in CVB3-infected mice. At later time points (day 42), there was a significant decrease in ACh-induced vasodilation in CVB3-infected mice. Bosentan, an ET-1 (ETA and ETB) receptor antagonist, did not completely ameliorate the reduced ACh-induced vasodilation in 42-day infected mice, indicating that ET-1 does not contribute to vascular dysfunction. Smooth muscle function, as measured by constriction to KCl or dilation to sodium nitroprusside, was unchanged in infected mice at early and late time points. Immunohistochemistry and ET-1 immunoassay were then performed to assess ET-1 levels in CVB3- and sham-infected hearts. There were no differences in ET-1 protein localization or levels at 42 days post infection in sham- and CVB3-infected animals. Finally, in situ hybridization and TUNEL staining were performed to assess viral localization and cell death in CVB3-infected hearts. There was no detectable CVB3 or TUNEL positivity in the endothelium of coronary arteries. Therefore, late impairment of endothelial-dependent vasorelaxation of coronary resistance vessels in CVB3-induced myocarditis does not appear to involve altered ET-1 expression but may be secondary to decreased stimulated NO secretion by the endothelium.

Acetylcholine↗