Coenzyme q10 prevents apoptosis by inhibiting mitochondrial depolarization independently of its free radical scavenging property.

The permeability transition pore (PTP) is a mitochondrial channel whose opening causes the mitochondrial membrane potential (deltapsi) collapse that leads to apoptosis. Some ubiquinone analogues have been demonstrated previously to modulate the PTP open-closed transition in isolated mitochondria and thought to act through a common PTP-binding site rather than through oxidation-reduction reactions. We have demonstrated recently both in vitro and in vivo that the ubiquitous free radical scavenger and respiratory chain coenzyme Q10 (CoQ10) prevents keratocyte apoptosis induced by excimer laser irradiation more efficiently than other antioxidants. On this basis, we hypothesized that the antiapoptotic property of CoQ10 could be independent of its free radical scavenging ability and related to direct inhibition of PTP opening. In this study, we have verified this hypothesis by evaluating the antiapoptotic effects of CoQ10 in response to apoptotic stimuli, serum starvation, antimycin A, and ceramide, which do not generate free radicals, in comparison to control, free radical-generating UVC irradiation. As hypothesized, CoQ10 dramatically reduced apoptotic cell death, attenuated ATP decrease, and hindered DNA fragmentation elicited by all apoptotic stimuli. This was accompanied by inhibition of mitochondrial depolarization, cytochrome c release, and caspase 9 activation. Because these events are consequent to mitochondrial PTP opening, we suggest that the antiapoptotic activity of CoQ10 could be related to its ability to prevent this phenomenon

Lipoprotein(a) and the risk of recurrent events in patients with acute myocardial infarction treated by percutaneous coronary intervention

Background: The role of Lipoprotein(a) (Lp[a]) in risk stratification following an acute myocardial infarction (AMI) is still debated. We aimed to investigate whether elevated Lp(a) levels in patients with AMI treated by percutaneous coronary intervention (PCI) are associated with worse outcomes. Methods: We designed a retrospective registry including patients with AMI undergoing PCI. The occurrence of major adverse cardiac and cerebrovascular events (MACCE), defined as death from cardiovascular causes, recurrent myocardial infarction, unplanned coronary revascularization and stroke, was assessed at follow up and compared between patients with high (≥ 30 mg/dl) and low (< 30 mg/dl) Lp(a) levels. Cox proportional hazard analysis was performed in order to assess independent predictors of MACCE. Results: During a 3-year period (2018-2020) we identified 634 patients with AMI treated by PCI and known Lp(a) blood levels; follow up visits were performed in 414 patients (median length 29 months [19-38]). Median Lp(a) level was 18 mg/dl [8-42]. The incidence of MACCE was significantly higher in high as compared to low Lp(a) group (log-rank p=0.018). The following independent predictors were identified at multivariate Cox regression: Lp(a) ≥30 mg/dl (HR 1.82 [95% CI 1.04-3.19], peripheral artery disease (HR 4.62 [95% CI 2.50-8.54]), number of diseased coronary vessels (HR 1.51 [95% 1.03-2.24] and presence of a coronary chronic total occlusion at coronary angiography (HR 3.46 [95% CI 1.77-6.76]). Conclusions: In this study, Lp(a) values ≥30 mg/dl were associated to worse outcomes in patients with AMI receiving PCI. Lp(a) could represent a useful tool to identify patients at high risk of recurrent events