Sahmin Lee

Adenylyl cyclase-associated protein 1 is a receptor for human resistin and mediates inflammatory actions of human monocytes.

Human resistin is a cytokine that induces low-grade inflammation by stimulating monocytes. Resistin-mediated chronic inflammation can lead to obesity, atherosclerosis, and other cardiometabolic diseases. Nevertheless, the receptor for human resistin has not been clarified. Here, we identified adenylyl cyclase-associated protein 1 (CAP1) as a functional receptor for human resistin and clarified its intracellular signaling pathway to modulate inflammatory action of monocytes. We found that human resistin directly binds to CAP1 in monocytes and upregulates cyclic AMP (cAMP) concentration, protein kinase A (PKA) activity, and NF-κB-related transcription of inflammatory cytokines. Overexpression of CAP1 in monocytes enhanced the resistin-induced increased activity of the cAMP-dependent signaling. Moreover, CAP1-overexpressed monocytes aggravated adipose tissue inflammation in transgenic mice that express human resistin from their monocytes. In contrast, suppression of CAP1 expression abrogated the resistin-mediated inflammatory activity both in vitro and in vivo. Therefore, CAP1 is the bona fide receptor for resistin leading to inflammation in humans.

Adipokine resistin is a key player to modulate monocytes, endothelial cells, and smooth muscle cells, leading to progression of atherosclerosis in rabbit carotid artery.

OBJECTIVES We investigated the effects of human resistin on atherosclerotic progression and clarified its underlying mechanisms. BACKGROUND Resistin is an adipokine first identified as a mediator of insulin resistance in murine obesity models. But, its role in human pathology is under debate. Although a few recent studies suggested the relationship between resistin and atherosclerosis in humans, the causal relationship and underlying mechanism have not been clarified. METHODS We cloned rabbit resistin, which showed 78% identity to human resistin at the complementary deoxyribonucleic acid level, and its expression was examined in 3 different atherosclerotic rabbit models. To evaluate direct role of resistin on atherosclerosis, collared rabbit carotid arteries were used. Histological and cell biologic analyses were performed. RESULTS Rabbit resistin was expressed by macrophages of the plaque in the 3 different atherosclerotic models. Peri-adventitial resistin gene transfer induced macrophage infiltration and expression of various inflammatory cytokines, resulting in the acceleration of plaque growth and destabilization. In vitro experiments elucidated that resistin increased monocyte-endothelial cell adhesion by upregulating very late antigen-4 on monocytes and their counterpart vascular cell adhesion molecule-1 on endothelial cells. Resistin augmented monocyte infiltration in collagen by direct chemoattractive effect as well as by enhancing migration toward monocyte chemotactic protein-1. Administration of connecting segment-1 peptide, which blocks very late antigen-4 × vascular cell adhesion molecule-1 interaction, ameliorated neointimal growth induced by resistin in vivo. CONCLUSIONS Our results indicate that resistin aggravates atherosclerosis by stimulating monocytes, endothelial cells, and vascular smooth muscle cells to induce vascular inflammation. These findings provide the first insight on the causal relationship between resistin and atherosclerosis.

Subclinical Coronary Artery Disease as Detected by Coronary Computed Tomography Angiography in an Asymptomatic Population

Background and Objectives Primary prevention of coronary artery disease (CAD) has become a public health issue, according to increasing awareness of the substantial risks posed by asymptomatic atherosclerosis. The aims of this study were to determine the prevalence and characteristics of subclinical CAD using coronary computed tomography angiography (CCTA), and to evaluate the role of this advanced technology in identifying subclinical CAD in asymptomatic Korean individuals, compared with conventional risk stratification. Subjects and Methods We enrolled 4,320 consecutive asymptomatic individuals (61% males, aged 50±9 years), who underwent 64-slice CCTA during a routine health check. Results Coronary artery plaques were present in 1,053 (24%) individuals. Significant stenosis (diameter stenosis ≥50%) was identified in 139 (3%) subjects, and most of the significant lesions (87%) were located in the left anterior descending artery. CCTA revealed noncalcified plaques in 5% of subjects with a coronary calcium score of zero (n=801). Although 25% (n=10) of those with noncalcified plaque had significant stenosis, most of them (90%) were classified into low- or moderate-risk groups according to National Cholesterol Education Program risk stratification guidelines. In a young population (age ≤55 years for males, ≤65 years for females), 30% of subjects with significant stenosis were classified into a low-risk group and 60% had low (0 to 100) calcium scores. Conclusion Subclinical CAD in asymptomatic individuals cannot be ignored for its considerable prevalence, CCTA may be helpful in identifying at-risk subclinical CAD in a noninvasive manner, especially in the young and traditionally low-risk population.

Angiographic patterns of restenosis with 2nd generation drug-eluting stent: comparative analysis from a 10-year single-center experience .

The angiographic features of restenosis contain prognostic information. However, restenosis patterns of the new generation drug-eluting stents (DES), everolimus-(EES) and resolute zotarolimus-eluting stent (ZES) have not been described.A total of 210 consecutive patients with DES restenosis were enrolled from 2003 to 2012. We analyzed 217 restenotic lesions after DES implantation, and compared the morphologic characteristics of the 2nd generation DES restenosis to those of restenosis with 2 first generation DES, sirolimus-(SES) and paclitaxel-eluting stent (PES).Baseline characteristics were comparable between the different stent groups. The incidence of focal restenosis was significantly lower for PES than the other stents (49.5% versus 87.0%, 76.2%, and 82.1% for PES versus SES, EES, and ZES, respectively, P < 0.001). When considering the pattern of restenosis solely within the stent margins, a further clear distinction between PES and other stents was observed (40.0% versus 92.9%, 88.9%, and 81.2% in PES versus SES, EES, and ZES, respectively, P < 0.001). There were no significant differences in restenosis patterns among SES, EES, and ZES. In multivariate analysis, PES implantation, hypertension, and age were associated with non-focal type of restenosis after DES implantation. After the introduction of EES and ZES into routine clinical practice in 2008, focal restenosis significantly increased from 63.9% to 76.7% and diffuse restenosis significantly decreased from 26.4% to 11.0% (P = 0.045).Focal restenosis was the most common pattern of restenosis in the new generation DES and the incidence of diffuse restenosis significantly decreased with the introduction of the 2nd generation DES.

Stentablation of an underexpanded stent in a heavily calcified lesion using rotational atherectomy.

To the Editor Adjunctive technologies such as high-speed mechanical rotational atherectomy [(Rotablator), Boston Scientific Corporation, Natick, Massachusetts, USA] are useful in augmenting the results of percutaneous coronary intervention in certain situations. Although data from randomized prospective trials are scarce, it is generally accepted that Rotablator therapy can be useful in preparation of

Coronary computed tomography angiography alone versus confirmatory functional testing for guiding treatment strategy for patients with intermediate coronary artery stenosis.

Intermediate coronary artery stenosis (≥50% and <90%) on coronary computed tomography angiography (CTA) is usually considered as a significant lesion. However, anatomical diagnosis is not well correlated with the functional significance of myocardial ischemia. We investigated whether functional testing in addition to coronary CTA improves outcomes of patients with intermediate stenosis, compared with the 1-step CTA-alone-based strategy. From 2006 to 2011, we consecutively enrolled 335 patients with chest pain with intermediate stenosis detected by an initially performed coronary CTA. Of these, 159 patients followed the 1-step strategy, whereas 176 followed the 2-step strategy with confirmatory functional tests. One-year follow-up data were obtained for all patients. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, and repeated or delayed revascularization (major adverse cardiac event) within a year. Baseline clinical parameters were comparable between patients of the 2 different strategies. The rate of invasive catheterization or percutaneous intervention was 75.5% in the 1-step group and 35.2% in the 2-step group (p <0.001). Consequently, more patients in the 2-step group were medically treated without unnecessary revascularization compared with patients in the 1-step group (71.0% vs 40.9%, p <0.001). Only 2.5% of the patients who received medical treatment in the 2-step group finally received delayed revascularization, whereas 14% in the 1-step group did. Overall, the primary end point occurred in 11.3% in the 1-step group and 4.0% in the 2-step group (p = 0.011). In conclusion, confirmatory functional testing reduces invasive catheterization and coronary intervention and improves clinical outcomes in patients with intermediate stenosis on coronary CTA.

NOT MYOCARDIAL PERFUSION STATUS ITSELF, BUT ITS FINAL HEMODYNAMIC CONSEQUENCE IS RELATED TO MYOCARDIAL SYSTOLIC FUNCTION IN HYPERTROPHIC CARDIOMYOPATHY: INTEGRATED APPROACH WITH ECHOCARDIOGRAPHY AND CARDIAC MAGNETIC RESONANCE IMAGING

Microvascular dysfunction is considered to play a crucial role in decreased coronary flow reserve (CFR), and to be related to myocardial functional changes in patients with hypertrophic cardiomyopathy (HCM) having normal coronary arteries. In this study, we aimed to determine in HCM 1) myocardial

SILDENAFIL INHIBITS VASCULAR SMOOTH MUSCLE CELL PROLIFERATION AND PLATELET AGGREGATION VIA ACTIVATION OF PROTEIN KINASE G (PKG), RESULTING IN REDUCING NEOINTIMAL HYPERPLASIA AFTER ANGIOPLASTY

Sildenafil has shown its effect in reducing cardiac hypertorphy as well as improving erectile dysfunction through Protein Kinase G (PKG) activation. Some studies have demonstrated that PKG occupies a central switching role in modulating vascular smooth muscle cell (VSMC) phenotype in response to

CORONARY CT ALONE VERSUS CONFIRMATORY FUNCTIONAL TEST FOR GUIDING PERCUTANEOUS CORONARY INTERVENTION OF INTERMEDIATE STENOSIS

Background: Intermediate stenosis (severity ≥50% and <90%) on coronary computed tomographic angiography (CTA) is usually considered as signiicant. However, luminal stenosis severity of coronary CTA is not well correlated with the functional signiicance of myocardial ischemia on noninvasive functional test or fractional low reserve (FFR) measurement. It is unclear whether routine test of functional signiicance in addition to coronary CTA improves outcomes in patients with intermediate lesions who are undergoing percutaneous coronary intervention (PCI).