Takayasu Kanno

Prostaglandin I2 promotes recruitment of endothelial progenitor cells and limits vascular remodeling

Objective—Endothelial progenitor cells (EPCs) play an important role in the self-healing of a vascular injury by participating in the reendothelialization that limits vascular remodeling. We evaluated whether prostaglandin I2 plays a role in the regulation of the function of EPCs to limit vascular remodeling. Methods and Results—EPCs (Lin−cKit+Flk-1+ cells) were isolated from the bone marrow (BM) of wild-type (WT) mice or mice lacking the prostaglandin I2 receptor IP (IP−/− mice). Reverse transcription–polymerase chain reaction analysis showed that EPCs among BM cells specifically express IP. The cellular properties of EPCs, adhesion, migration, and proliferation on fibronectin were significantly attenuated in IP-deficient EPCs compared with WT EPCs. In contrast, IP agonists facilitated these functions in WT EPCs, but not in IP-deficient EPCs. The specific deletion of IP in BM cells, which was performed by transplanting BM cells of IP−/− mice to WT mice, accelerated wire injury–mediated neointimal hyperplasia in the femoral artery. Notably, transfused WT EPCs, but not IP-deficient EPCs, were recruited to the injured vessels, participated in reendothelialization, and efficiently rescued the accelerated vascular remodeling. Conclusion—These findings clearly indicate that the prostaglandin I2-IP system is essential for EPCs to accomplish their function and plays a critical role in the regulation of vascular remodeling.

Late gadolinium enhancement on cardiac magnetic resonance represents the depolarizing and repolarizing electrically damaged foci causing malignant ventricular arrhythmia in hypertrophic cardiomyopathy

BACKGROUND The presence of a myocardial scar detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) has been described as a predictor of all-cause mortality in hypertrophic cardiomyopathy (HCM). However, the detailed spatial relationship between LGE site and electrical abnormality is unclear in high-risk HCM with malignant arrhythmia. OBJECTIVE The purpose of this study was to elucidate the detailed relationship between the site on CMR imaging and the electrically damaged site, a potential origin of ventricular arrhythmias in patients with HCM. METHODS Fifty consecutive HCM patients underwent contrast-enhanced CMR. Of those patients, 18 patients with ventricular tachycardia underwent electrophysiology study including endocardial mapping of the left ventricle (LV). The LGE area was calculated at 12 different LV sites: anterior, lateral, posterior, and septal segments of the basal, middle, and apical portions. At each LV site, the bipolar electrogram, effective refractory period (ERP), and monophasic action potential were recorded. RESULTS LGE-positive segments demonstrated a significantly lower amplitude (4.0 ± 2.8 mV vs 7.3 ± 3.6 mV; P < .001), longer duration (54.7 ± 17.8 vs 40.6 ± 7.8 ms; P < .001), longer ERP (320 ± 42 ms vs 284 ± 37 ms; P = .001), and longer monophasic action potential duration measured at 90% repolarization (321 ± 19 ms vs 283 ± 25 ms; P < .001) than did LGE-negative segments. The LGE area negatively correlated with the amplitude (r = -0.59; P < .001) and positively correlated with the duration (r = 0.64; P < .001), ERP (r = 0.44; P < .001), and action potential duration measured at 90% repolarization (r = 0.63; P < .001). All the observed VTs originated from LGE-positive segments. CONCLUSION The spatial distribution of LGE significantly correlates with depolarizing and repolarizing electrical damage in high-risk HCM with malignant ventricular arrhythmia.