Rationale: While cell-cell interaction plays a critical role in physiology and disease, a comprehensive understanding of its dynamics in vascular homeostasis and diseases is yet absent. Methods: Here, by use of single-cell RNA-sequencing and multi-color staining, we delineate the cellular composition and spatial characterization of human aorta with or without aortic dissection (AD). Results: Scrutinization of cell subtype alterations revealed significantly changed fibroblast (FB)-smooth muscle cell (SMC) interactions in AD. Of these cellular interactions, LOX high fibroblast (fibroblast subtype 2, FB2) in diseased state exerted the most pronounced effects on pathological deterioration of SMCs in AD. In addition, pharmacologically targeting the BMP (bone morphogenetic protein) signaling pathway effectively suppressed FB2 state transition and reduced AD incidence in mice. Finally, COL5A1 (collagen type V alpha 1 chain), one of the secreted proteins released from FB2, was significantly higher in the plasma of AD patients than in control patients, suggesting its potential use as a biomarker for AD diagnosis. Conclusions: Our work not only identified a pivotal role of a specific FB subtype in AD progression, but also shed light on cell interaction dynamics in vascular diseases.
Intra-myocardial injection of aBMMNC transplantation on arrested heart during CABG is a safe procedure based on a longer period observation. The patients with chronic ischemic heart failure can benefit from aBMMNCs transplantation in the short-term (6 months) demonstrated by improved global LVEF compared with the control group; however, this additional benefit dimed with time as showed by 24-month clinical and echocardiographic follow-up results.
Background:The optimal timing of surgical revascularization for patients presenting with ST-segment elevation myocardial infarction (STEMI) and impaired left ventricular function is not well established. This study aimed to examine the timing of surgical revascularization after STEMI in patients with ischemic heart disease and left ventricular dysfunction (LVD) by comparing early and late results.Methods:From January 2003 to December 2013, there were 2276 patients undergoing isolated coronary artery bypass grafting (CABG) in our institution. Two hundred and sixty-four (223 male, 41 females) patients with a history of STEMI and LVD were divided into early revascularization (ER, <3 weeks), mid-term revascularization (MR, 3 weeks to 3 months), and late revascularization (LR, >3 months) groups according to the time interval from STEMI to CABG. Mortality and complication rates were compared among the groups by Fisher's exact test. Cox regression analyses were performed to examine the effect of the time interval of surgery on long-term survival.Results:No significant differences in 30-day mortality, long-term survival, freedom from all-cause death, and rehospitalization for heart failure existed among the groups (P > 0.05). More patients in the ER group (12.90%) had low cardiac output syndrome than those in the MR (2.89%) and LR (3.05%) groups (P = 0.035). The mean follow-up times were 46.72 ± 30.65, 48.70 ± 32.74, and 43.75 ± 32.43 months, respectively (P = 0.716). Cox regression analyses showed a severe preoperative condition (odds ratio = 7.13, 95% confidence interval 2.05–24.74, P = 0.002) rather than the time interval of CABG (P > 0.05) after myocardial infarction was a risk factor of long-term survival.Conclusions:Surgical revascularization for patients with STEMI and LVD can be performed at different times after STEMI with comparable operative mortality and long-term survival. However, ER (<3 weeks) has a higher incidence of postoperative low cardiac output syndrome. A severe preoperative condition rather than the time interval of CABG after STEMI is a risk factor of long-term survival.
Summary.We evaluated the effect of trimetazidine (TMZ) on recovery of regional cardiac function in anesthetized open-chest pigs, subjected to fifteen 2-minute occlusions of the left anterior descending coronary artery, separated by 2 minutes of reperfusion and a 120-minute recovery period. Regional myocardial function was evaluated by sonomicrometry-derived segment lengthening and the area enclosed by the left ventricular pressure-segment length loop (external work, EW) in animals, which received either an intracoronary infusion of TMZ (33 ~tg/kg/min, n = 6) or saline (1 ml/ min, n = 7), starting 15 minutes before the first occlusion and ending 2 minutes after the 15th occlusion. In addition, myocardial malondialdehyde production to evaluate oxygen free radical production, oxygen consumption, and the ATP, ADP, and AMP content, as well as the energy charge, were determined at regular time intervals.In control pigs the sequences of occlusion-reperfusion did not affect systemic hemodynamics, except for the LVdP/ dtm~ x, which decreased by 11% during the interventions and did not recover during the following reperfusion period of 2 hours (78% of baseline, p < 0.05). Systolic segment length shortening and EW were increased at the end of the first ocelusion-reperfusion cycle, decreased gradually during the remainder of the ocelusion-reperfusion periods, and did not improve during the recovery period. Energy charge and myocardial blood flow were not impaired, but oxygen consumption was decreased during the recovery period. The malondialdeyde data did not provide evidence for production of oxygen free radicals. TMZ decreased LVdP/dt~ by 6% (p < 0.05) and caused a twofold increase in postsystolic segment shortening (p < 0.05) before the first occlusion, but did not influence the hemodynamic responses, the changes in regional cardiac function, and the metabolic events produced by repetitive regional ischemia.
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