Insight into the cardioprotective effects of melatonin: shining a spotlight on intercellular Sirt signaling communication.

Cardiovascular diseases (CVDs) are the leading causes of death and illness worldwide. While there have been advancements in the treatment of CVDs using medication and medical procedures, these conventional methods have limited effectiveness in halting the progression of heart diseases to complete heart failure. However, in recent years, the hormone melatonin has shown promise as a protective agent for the heart. Melatonin, which is secreted by the pineal gland and regulates our sleep-wake cycle, plays a role in various biological processes including oxidative stress, mitochondrial function, and cell death. The Sirtuin (Sirt) family of proteins has gained attention for their involvement in many cellular functions related to heart health. It has been well established that melatonin activates the Sirt signaling pathways, leading to several beneficial effects on the heart. These include preserving mitochondrial function, reducing oxidative stress, decreasing inflammation, preventing cell death, and regulating autophagy in cardiac cells. Therefore, melatonin could play crucial roles in ameliorating various cardiovascular pathologies, such as sepsis, drug toxicity-induced myocardial injury, myocardial ischemia-reperfusion injury, hypertension, heart failure, and diabetic cardiomyopathy. These effects may be partly attributed to the modulation of different Sirt family members by melatonin. This review summarizes the existing body of literature highlighting the cardioprotective effects of melatonin, specifically the ones including modulation of Sirt signaling pathways. Also, we discuss the potential use of melatonin-Sirt interactions as a forthcoming therapeutic target for managing and preventing CVDs.

Pivotal Role of TGF-ß/Smad Signaling in Cardiac Fibrosis: Non-coding RNAs as Effectual Players.

Unintended cardiac fibroblast proliferation in many pathophysiological heart conditions, known as cardiac fibrosis, results in pooling of extracellular matrix (ECM) proteins in the heart muscle. Transforming growth factor ß (TGF-ß) as a pivotal cytokine/growth factor stimulates fibroblasts and hastens ECM production in injured tissues. The TGF-ß receptor is a heterodimeric receptor complex on the plasma membrane, made up from TGF-ß type I, as well as type II receptors, giving rise to Smad2 and Smad3 transcription factors phosphorylation upon canonical signaling. Phosphorylated Smad2, Smad3, and cytoplasmic Smad4 intercommunicate to transfer the signal to the nucleus, culminating in provoked gene transcription. Additionally, TGF-ß receptor complex activation starts up non-canonical signaling that lead to the mitogen-stimulated protein kinase cascade activation, inducing p38, JNK1/2 (c-Jun NH2-terminal kinase 1/2), and ERK1/2 (extracellular signal-regulated kinase 1/2) signaling. TGF-ß not only activates fibroblasts and stimulates them to differentiate into myofibroblasts, which produce ECM proteins, but also promotes fibroblast proliferation. Non-coding RNAs (ncRNAs) are important regulators of numerous pathways along with cellular procedures. MicroRNAs and circular long ncRNAs, combined with long ncRNAs, are capable of affecting TGF-ß/Smad signaling, leading to cardiac fibrosis. More comprehensive knowledge based on these processes may bring about new diagnostic and therapeutic approaches for different cardiac disorders.

Stent underexpansion in angiographic guided percutaneous coronary intervention, despite adjunctive balloon post-dilatation, in drug eluting stent era.

BACKGROUND: Stent underexpansion is the most powerful predictor of long-term stent patency and clinical outcome. The purpose of this study was to evaluate the incidence and predictors of stent underexpansion despite adjunctive post-dilatation with non-compliant balloon. METHODS: After elective coronary stent implantation and adjunctive post-dilatation with non-compliant balloon and optimal angiographic result confirmed by the operator, intravascular ultrasound (IVUS) was performed for all the treated lesions. If the treated lesions fulfilled the IVUS criteria, they are considered as the optimal stent group; if not, they are considered as the suboptimal group. RESULTS: From 50 patients enrolled in this study 39 (78%) had optimal stent deployment and 11 (22%) had suboptimal stent deployment. In the suboptimal group 7 (14%) had underexpansion, 2 (4%) malposition, and 2 (4%) had asymmetry. There were no stent edge dissections detected by IVUS. We did not find any correlation between lesion calcification, ostial lesions, stent length, and stent underexpansion. Stent diameter ≤ 2.75 mm had a strong correlation with stent underexpansion. CONCLUSION: Despite adjunctive post-dilatation with noncompliant balloon, using a relatively small stent diameter was a strong predictor for underexpansion. IVUS guided percutaneous coronary intervention (PCI) may be considered for drug eluting stent (DES) implantation in relatively small vessels.