Epidemiologic data suggested that there was an obvious predominance of young adult patients with a slight female proneness in severe acute respiratory syndrome (SARS). The angiotensin-converting enzyme 2 (ACE2) was very recently identified as a functional receptor for SARS virus and is therefore a prime target for pathogenesis and pharmacological intervention. Rats of both genders at three distinct ages (young-adult, 3 months; middle-aged, 12 months; old, 24 months) were evaluated to determine the characteristic of ACE2 expression in lung and the effect of aging and gender on its expression. ACE2 was predominantly expressed in alveolar epithelium, bronchiolar epithelium, endothelium and smooth muscle cells of pulmonary vessels with similar content, whereas no obvious signal was detected in the bronchiolar smooth muscle cells. ACE2 expression is dramatically reduced with aging in both genders: young-adult vs. old P < 0.001 (by 78% in male and 67% in female, respectively) and middle-aged vs. old P < 0.001 (by 71% in male rats and 59% in female rats, respectively). The decrease of ACE2 content was relatively slight between young-adult and middle-aged groups (by 25% in male and 18% in female, respectively). Although there was no gender-related difference of ACE2 in young-adult and middle-aged groups, a significantly higher ACE2 content was detected in old female rats than male. In conclusion, the more elevated ACE2 in young adults as compared to aged groups may contribute to the predominance in SARS attacks in this age group.
This preliminary study showed that intravenous infusion of autologous EPCs seemed to be feasible and safe, and might have beneficial effects on exercise capacity and pulmonary hemodynamics in patients with IPAH. (Safety and Efficacy Study of Transplantation of EPCs to Treat Idiopathic Pulmonary Arterial Hypertension; http://www.clinicaltrials.gov/ct/show/NCT00257413?order=1; NCT00257413).
Our observations indicated that EPC numbers and functional capacity were impaired in patients with IPAH, which might not only give potential insight into the pathophysiological mechanisms but also might be useful for identifying suitable therapeutic targets in these patients.
BackgroundPatients with mixed hyperlipidemia usually are in need of combination therapy to achieve low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) target values for reduction of cardiovascular risk. This study investigated the efficacy and safety of adding a new hypolipidemic agent, coenzyme A (CoA) to stable statin therapy in patients with mixed hyperlipidemia.MethodsIn this multi-center, 8-week, double-blind study, adults who had received ≥8 weeks of stable statin therapy and had hypertriglyceridemia (TG level at 2.3-6.5 mmol/L) were randomized to receive CoA 400 U/d or placebo plus stable dosage of statin. Efficacy was assessed by the changes in the levels and patterns of lipoproteins. Tolerability was assessed by the incidence and severity of adverse events (AEs).ResultsA total of 304 patients with mixed hyperlipidemia were randomized to receive CoA 400 U/d plus statin or placebo plus statin (n = 152, each group). After treatment for 8 weeks, the mean percent change in TG was significantly greater with CoA plus statin compared with placebo plus statin (-25.9% vs -4.9%, respectively; p = 0.0003). CoA plus statin was associated with significant reductions in TC (-9.1% vs -3.1%; p = 0.0033), LDL-C (-9.9% vs 0.1%; p = 0.003), and non- high-density lipoprotein cholesterol (-13.5% vs -5.7%; p = 0.0039). There was no significant difference in the frequency of AEs between groups. No serious AEs were considered treatment related.ConclusionsIn these adult patients with persistent hypertriglyceridemia, CoA plus statin therapy improved TG and other lipoprotein parameters to a greater extent than statin alone and has no obviously adverse effect.Trial registrationCurrent Controlled Trials ClinicalTrials.gov ID
NCT01928342.
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