Current Vascular Pharmacology - Volume 23, Issue 5, 2025

Empagliflozin (EMPA), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), represents a novel therapeutic agent for diabetes management. Over the past decade, studies have consistently demonstrated that EMPA not only effectively lowers blood glucose levels but also confers substantial cardiovascular benefits without inducing hypoglycemia. This holds for individuals with or without diabetes, highlighting EMPA’s potential in mitigating the risk of adverse cardiovascular events and cardiovascular mortality. The underlying mechanisms driving these advantageous effects remain incompletely understood, with presently elucidated pathways encompassing blood pressure reduction, oxidative stress attenuation, anti-inflammatory properties, metabolic regulation, uric acid level modulation, inhibition of Na⁺/H⁺ exchangers, preservation of mitochondrial function, vascular protection, and regulation of myocardial autophagy. In this review, we considered the effects and mechanisms of EMPA in combating diabetic cardiomyopathy (DCM), underscoring its therapeutic relevance in addressing cardiovascular complications associated with diabetes.

With the aging population on the rise, the higher prevalence of atrial tachyarrhythmia is emerging as a significant healthcare concern. Atrial fibrillation (AF) stands out as the most common atrial tachyarrhythmia, potentially leading to adverse outcomes, such as stroke, heart failure (HF), or conduction dysfunction. Furthermore, AF may serve as a manifestation of underlying atrial cardiomyopathy, which forms the structural and electrical substrate for arrhythmias. Atrial cardiomyopathy is characterized by structural and electrical remodeling of the atria, resulting in impaired mechanical function and the generation of arrhythmias. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have recently emerged as a novel medical treatment for HF. Their use has been associated with a reduced incidence of new-onset AF, potentially attributing to the improvement of atrial cardiomyopathy. This effect is achieved through the regulation of glucose utilization and energy consumption within the myocardium. It is worth noting that the sirtuin signaling pathway plays a crucial role in regulating energy consumption, especially in the presence of increased oxidative stress and fibrosis. This pathway also exerts a significant influence on various cardiovascular diseases. This review aims to provide a comprehensive summary of the involvement of the sirtuin signaling pathway in cardiovascular diseases, with a specific focus on atrial cardiomyopathy and AF and the potential molecular mechanisms of SGLT2is in the sirtuin signaling pathway and atrial cardiomyopathy.

Resveratrol [RES] is a polyphenolic stilbene with therapeutic potential owing to its antioxidant, anti-inflammatory, neuroprotective, and cardioprotective properties. However, the very poor oral bioavailability, fast metabolism, and extremely low stability under physiological conditions pose a severe detriment to the clinical use of RES. This newly developed field of nanotechnology has led to the formulation of RES into nanoformulations with the goal of overcoming metabolic-pharmacokinetic limitations and enhancing the targeted transport of RES to the central nervous system [CNS]. Among the various routes of administration, the combination of nose-to-brain [N2B] delivery via the intranasal [IN] route has recently garnered attention as a straightforward, non-invasive route for transport to the blood-brain barrier [BBB] for greater effects and less harmful systemic side effects by transporting nano-encapsulated RES into the neural tissues. This review critically summarizes the mechanisms and benefits of the N2B route for the delivery of RES nanoformulations, collating in vivo data demonstrating increased CNS bioavailability and stability and, consequently, improved therapeutic efficacy in animal models of neurodegenerative diseases. Compared with the more 'traditional' routes of administration, IN administration of RES nanoformulations is less toxic, cost-effective, and efficient in crossing the BBB. Therefore, this route represents a promising approach to the management of CNS disorders. Further optimization of nanoformulation design and clinical protocols is required to translate these promising findings into therapeutic strategies aimed at neuroprotection and disease modification in human CNS pathologies.

Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and inherited vascular disorder characterized by the development of arteriovenous malformations (AVMs) in various organs and telangiectasia (small AVM) in the mucocutaneous. The majority of HHT patients have haploinsufficiency of genes involved in the transforming growth factor-beta (TGF-β) signaling pathway, including endoglin (ENG), activin receptor-like kinase 1 (ALK1, also known as ACVRL1), or SMAD4. Active angiogenesis is also required for telangiectasia and AVM development. Anti-angiogenic strategies have been tested in patients and animal models extensively. However, the exact mechanisms for telangiectasia and AVM development remain unclear. In this review, we discussed several important advances in the past 10 years in understanding HHT disease mechanisms and in therapeutic development.