Minerva cardioangiologica最新文献

Background: Increased oxidative stress potentially leads to accelerated atherosclerosis and, consequently, cardiovascular diseases, the main cause of death in systemic lupus erythematous (SLE). To gain insight into these mechanisms, we studied the association of uncoupling protein (UCP) 2 genetic variants, gene involved in the mitochondrial production of reactive oxygen species, and oxidative stress with SLE and the presence of atherosclerosis.

Methods: Genetic analysis of the UCP2 -866G/A and UCP2 Ins/Del polymorphisms was performed in 45 SLE patients and 36 healthy controls by RFLP-PCR. Oxidation status was determined by measuring malondialdehyde (MDA) levels. Presence of subclinical atherosclerosis was investigated by evaluation of intima-media thickness using echo-color-Doppler carotid ultrasound examination.

Results: Allelic and genotypic frequencies of the SNPs analysed were evaluated by gene count. Significant association was found between UCP2-866A allele and susceptibility for SLE (P=0.001). Higher levels of MDA were found significantly increased in SLE patients (MDA, 5.05±3.36 µmol/L) compared to normal controls (MDA, 2.79±0.89 µmol/L) (P<0.0001).

Conclusions: Our results suggest that -866G/A UCP2 polymorphism is associated with SLE causing increased ROS production that, in turn, results in increased MDA levels responsible of accelerated atherosclerosis.

Background: Nothofagin is a mono-C-glycoside of 4,2',4',6'-tetrahydroxy-dihydrochalcone that is commonly found in Aspalathus linearis, Nothofagus fusca, and Leandra dasytricha. A wide range of biological effects has been attributed to nothofagin, including antioxidant, diuretic, renoprotective, antiplatelet, and antithrombotic effects. Although nothofagin is pharmacologically active, its effects on blood pressure remain unknown. In the present study, we investigated whether nothofagin causes acute and prolonged hypotension in male Wistar rats, and we investigated the molecular mechanisms that underlie these hemodynamic effects.

Methods: Hypotensive effects of nothofagin (0.3, 1, and 3 mg/kg) were evaluated after acute intraduodenal administration and after 7 days of oral treatment. Using pharmacological antagonists and inhibitors, we explored the involvement of the prostaglandin/cyclic adenosine monophosphate and nitric oxide/cyclic guanosine monophosphate pathways and K⁺ channels in nothofagin-induced hypotension.

Results: Acute and prolonged nothofagin administration significantly decreased systolic blood pressure and mean arterial pressure in Wistar rats. Pretreatment with N(G)-nitro-L-arginine methyl ester, methylene blue, and tetraethylammonium prevented the hypotensive effect of nothofagin.

Conclusions: These results show that nothofagin induces a hypotensive response in Wistar rats, and this effect depends on K⁺ channel opening in smooth muscle cells through nitric oxide signaling.

Although initially introduced as a novel oral glucose-lowering agent class, cumulative evidence from randomized controlled trials (RCTs) have led sodium-glucose cotransporter-2 inhibitors (SGLT2i) to become a component of primary and secondary prevention from atherosclerotic cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Dapagliflozin, one of the agents of this class, was investigated in 2019 in patients with heart failure (HF) independent of being diagnosed with T2DM at baseline. Since then, many other studies are being undertaken in this class of drugs. Herein, we aimed to review the RCTs, their subgroup and post-hoc analyses that examined the effects of SGLT2i on cardiovascular outcomes (including HF-related outcomes) in patients diagnosed with HF that were published until June 2020. We also summarized the ongoing trials that aim to assess the impact of SGLT2i on cardiovascular outcomes in patients with HF and listed available guideline recommendations regarding the use of SGLT2i for cardiovascular disease management.