Tae Jin Youn

Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node function and connexin 45 localization in the murine heart

The coxsackievirus and adenovirus receptor (CAR) is a transmembrane protein that belongs to the family of adhesion molecules. In the postnatal heart, it is localized predominantly at the intercalated disc, where its function is not known. Here, we demonstrate that a first degree or complete block of atrioventricular (AV) conduction developed in the absence of CAR in the adult mouse heart and that prolongation of AV conduction occurred in the embryonic heart of the global CAR-KO mouse. In the cardiac-specific CAR-KO (CAR-cKO) mouse, we observed the loss of connexin 45 localization to the cell-cell junctions of the AV node but preservation of connexin 40 and 43 in contracting myocardial cells and connexin 30.2 in the AV node. There was also a marked decrease in beta-catenin and zonula occludens-1 (ZO-1) localization to the intercalated discs of CAR-cKO mouse hearts at 8 weeks before the mice developed cardiomyopathy at 21 weeks of age. We also found that CAR formed a complex with connexin 45 via its PSD-95/DigA/ZO-1-binding (PDZ-binding) motifs. We conclude that CAR expression is required for normal AV-node conduction and cardiac function. Furthermore, localization of connexin 45 at the AV-node cell-cell junction and of beta-catenin and ZO-1 at the ventricular intercalated disc are dependent on CAR.

A Novel Biomarker of Coronary Atherosclerosis: Serum DKK1 Concentration Correlates with Coronary Artery Calcification and Atherosclerotic Plaques

DKK1 modulates Wnt signaling, which is involved in the atherosclerosis. However, no data exist regarding the usefulness of measuring serum DKK1 concentration in predicting coronary atherosclerosis. A total of 270 consecutive patients (62.8 ± 11.2 yr; 70% male) were included. A contrast-enhanced 64-slice coronary MDCT was performed to identify the presence of atherosclerotic plaques. Agatston calcium scores (CS) were calculated to quantify the coronary artery calcification (CAC). DKK1 concentrations were measured by enzyme-linked immunosorbent assay. For each subsequent DKK1 quartile, there was a significant increase in CAC (P = 0.004) and the number of segments with coronary atherosclerosis (P < 0.001). In addition, DKK1 concentration was significantly higher in patients with atherosclerotic plaques, regardless of plaque composition (P = 0.01). Multivariate analysis identified DKK1 as an independent risk factor for the presence of coronary atherosclerotic plaque. The adjusted odds ratio for coronary atherosclerotic plaque was 4.88 (95% CI, 1.67 to 14.25) for highest versus lowest quartile of the DKK1 levels. Furthermore, patients with DKK1 concentrations ≥ 68.6 pg/mL demonstrated coronary atherosclerotic plaques even when they had low CS. Serum DKK1 concentrations correlate with the coronary atherosclerosis and play an independent role in predicting the presence of coronary atherosclerosis.

Immediate multivessel revascularization may increase cardiac death and myocardial infarction in patients with ST-elevation myocardial infarction and multivessel coronary artery disease: data analysis from real world practice.

Background/Aims: The best revascularization strategy for patients with both acute ST-elevation myocardial infarction (STEMI) and multivessel coronary disease (MVD) is still debatable. We aimed to compare the outcomes of multivessel revascularization (MVR) with those of culprit-only revascularization (COR). Methods: A cohort of 215 consecutive patients who had received primary angioplasty for STEMI and MVD were divided into two groups according to whether angioplasty had been also performed for a stenotic nonculprit artery. The primary endpoint was one-year major adverse cardiac events defined as a composite of cardiac death, recurrent myocardial infarction, or any repeat revascularization. Results: One-year major adverse cardiac events were not significantly different between MVR (n = 107) and COR (n = 108) groups. However, the one-year composite hard endpoint of cardiac death or recurrent myocardial infarction was notably increased in the MVR group compared to the COR group (20.0% vs. 8.9%, p = 0.024). In subgroup analysis, the hard endpoint was significantly more frequent in the immediate than in the staged MVR subgroup (26.6% vs. 9.8%, p = 0.036). The propensity score-matched cohorts confirmed these findings. Conclusions: In patients with STEMI and MVD, MVR, especially immediate MVR with primary percutaneous intervention, was not beneficial and led to worse outcomes. Therefore, we conclude that COR or staged MVR would be better strategies for patients with STEMI and MVD.

Diagnostic accuracy of manual office blood pressure measurement in ambulatory hypertensive patients in Korea

Background/Aims Currently, office blood pressure (OBP) is the most widely used method of measuring blood pressure (BP) in daily clinical practice. However, data on the diagnostic accuracy of OBP in reference to ambulatory blood pressure (ABP) are scarce in Korea. Methods In retrospective and prospective cohorts, manual OBP and ABP measurements were compared among ambulatory hypertensive patients. Hypertension was defined as systolic OBP ≥ 140 mmHg and/or diastolic OBP ≥ 90 mmHg, and systolic ABP ≥ 130 mmHg and/or diastolic ABP ≥ 80 mmHg. Results In the retrospective cohort (n = 903), the mean OBP1 (before ABP measurement) was higher than ABP in both systolic (138 ± 17 mmHg vs. 123 ± 13 mmHg, p < 0.001) and diastolic (84 ± 12 mmHg vs. 78 ± 11 mmHg, p < 0.001) measurements. Interestingly, there was only a weak correlation between OBP and ABP (r2 = 0.038, p < 0.001). The overall discordance rate of OBP compared to ABP, which is the reference method for measuring BP, was 43.9%. The prospective cohort (n = 57) showed similar results. In a subgroup analysis, male patients had higher false negative results (masked or under-treated hypertension) than did female patients (26.1% vs. 17.8%, p = 0.003), whereas female patients had a higher false positive rate (white-coat or over-treated hypertension) than did male patients (28.7% vs. 15.2%, p < 0.001). Conclusions The diagnostic accuracy of manual OBP is low in reference to ABP. Men and women have different patterns of discordance. These findings indicate that management of hypertensive patients with manual OBP measurements may be suboptimal and encourages the use of ABP in ambulatory hypertensive patients.