PET evaluation of myocardial perfusion function after percutaneous coronary intervention in patients with chronic total occlusion: a systematic review and meta-analysis.

Objective. The benefit of percutaneous coronary intervention (PCI) in chronic complete coronary artery occlusion (CTO) remains controversial. PCI is currently indicated only for symptom and myocardial ischemia abolition, but large chronically occluded vessels with extensive afferent myocardial territories may benefit most from this procedure. The noninvasive evaluation of myocardial perfusion is critical before and after revascularization, and positron emission tomography (PET) can determine absolute myocardial perfusion. Here, we aimed to explore and compare myocardial perfusion in CTO territories and their remote associated areas before and after PCI. Design. We searched for relevant articles published before November 28, 2022, in the Cochrane Library and PubMed. We calculated 95% confidence intervals (CIs) and standardized mean differences (SMDs) for parameters related to myocardial perfusion in CTO territories and remote areas in CTO patients before and after PCI. Results. We included five studies published between 2017 and 2022, with a total of 592 patients. Stress myocardial blood flow (MBF) was increased in CTO territories after PCI when compared to pre-PCI (mean difference [MD]: 1.70, 95% confidence interval [CI] 1.33-2.08, p < 0.001). Coronary flow reserve (CFR) in CTO regions was also higher after PCI (MD 1.37,95% [CI]1.13-1.61, p < 0.001). Stress MBF in remote regions was also increased after PCI (MD 0.27,95% [CI]0.99 ∼ 0.45, p = 0.004), as was CFR in remote regions (MD 0.32,95% [CI] 0.14-0.5, p = 0.001). Conclusions. According to our pooled analysis of current literature, there was an increase in stress MBF and CFR in both CTOs and remote regions after PCI, suggesting that patients with CTO have widespread recovery of blood perfusion after the procedure. These results provide evidence that patients with CTO arteries and high ischemic burdens would indeed benefit from CTO-PCI. Future research on the correlation of ischemia burden reduction with hard clinical endpoints would contribute to a clearer demarcation of the role of CTO PCI with prognostic potential.

The therapeutic efficacy and clinical translation of mesenchymal stem cell-derived exosomes in cardiovascular diseases.

Exosomes, mainly derived from mesenchymal stem cells, provide a good reference for cardiac function repair and clinical application in cardiac and vascular diseases by regulating cardiomyocyte viability, inflammatory levels, angiogenesis, and ventricular remodeling after a heart injury. This review presents the cardioprotective efficacy of mesenchymal stem cell-originated exosomes and explores the underlying molecular mechanisms. Furthermore, we expound on several efficient approaches to transporting exosomes into the heart in clinical application and comment on the advantages and disadvantages of each method.

Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Alleviate Diabetic Kidney Disease in Rats by Inhibiting Apoptosis and Inflammation.

BACKGROUND AND AIMS: Previous studies have confirmed the anti-inflammation effect of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo). We aimed to investigate the therapeutic effect of BMSC-Exo on diabetic kidney disease (DKD), as well as the underlying mechanisms. METHODS: SD rats were induced by streptozotocin combined with a high-fat diet to establish a diabetes disease model. BMSCs-Exo were injected via tail veins at a weekly dose of 100 µg for 12 weeks. Pathological changes in the rat kidneys were evaluated using HE, Masson, and Periodic Acid-Schiff and immunohistochemical staining. TUNEL staining and western blot were used to evaluate the expression levels of apoptosis-related proteins in the rat kidney cells. The TNF-α level was detected by PCR and NF-κB (p65) by western blotting to examine the inflammatory responses in the renal tissue. RESULTS: BMSCs-Exo significantly alleviated the renal structural damage and the distribution of apoptotic cells in diabetic rats. Furthermore, BMSCs-Exo increased the expression of pro-apoptosis protein Bax and decreased the expression of apoptosis-executing protein Cleaved Caspase 9 and Cleaved caspase 3. In addition, the transcription level of TNF-α in kidney tissue and NF-κB (p65) expression was also decreased through BMSCs-Exo treatment. Besides, the levels of glucose (GLU), creatinine (Cr), and burea nitrogen (BUN) in diabetic rats were decreased by the BMSC-Exo treatment. CONCLUSIONS: BMSCs-Exo may alleviate diabetic kidney damage by inhibiting apoptosis and inflammation.

Regulation of cardiovascular and cardiac functions by caveolins.

Caveolae are intracellular vesicles with diameters ranging from 50 to 100 nm. The role of caveolins in mediating oxidative stress, autophagy, apoptosis, fibrosis, and vascular remodeling has attracted increasing attention in cardiovascular therapy. Several studies have suggested that caveolin could be a therapeutic target for the treatment of cardiac and/or vascular injury via several pathophysiological mechanisms. Despite substantial advances in our understanding of the basic biology of vesicles over the past decade, the relevance and specific role of these mechanisms in cardiovascular homeostasis remains ambiguous. Here, we review the macroscopic role of caveolins in protecting cardiac function and, at the microscopic level, examine possible cardioprotective caveolar mechanisms, including their antioxidative stress, antiapoptosis, autophagy-regulatory, antifibrosis, and angiogenesis-promoting properties. We believe that the role of caveolins in cardiac functioning has not been fully elucidated and is an important line of future research with several cardioprotective implications.

Ginkgo biloba extract protects against diabetic cardiomyopathy by restoring autophagy via adenosine monophosphate-activated protein kinase/mammalian target of the rapamycin pathway modulation.

Studies demonstrated that Ginkgo biloba extract (GBE) played a cardioprotective role in diabetic conditions. Impaired autophagy is one of the mechanisms underlying diabetic cardiomyopathy (DCM). The effect of GBE on autophagy has been observed in several diseases; however, whether GBE can ameliorate DCM by regulating autophagy remains unclear. Here, we investigated the effect of GBE on DCM and the potential mechanisms regarding autophagy using a streptozotocin (STZ)-induced diabetic rat model and a high-glucose (HG)-stimulated H9C2 cell model. We demonstrated that GBE attenuated metabolic disturbances, improved cardiac function, and reduced myocardial pathological changes in diabetic rats. Impaired autophagy as well as dysregulation of the adenosine monophosphate-activated protein kinase/ mammalian target of the rapamycin (AMPK/mTOR) signaling pathway were observed in diabetic hearts, as evidenced by the reduced conversion of LC3B-I to LC3B-II along with excessive p62 accumulation, decreased AMPK phosphorylation, and increased mTOR phosphorylation, which could be reversed by GBE treatment. In vitro, GBE reduced the apoptosis induced by HG in H9C2 cells by activating AMPK and inhibiting mTOR to restore autophagy. However, this effect was inhibited by the AMPK inhibitor Compound C. In conclusion, the ameliorative effect of GBE on DCM might be dependent on the restoration of autophagy through modulation of the AMPK/mTOR pathway.

Exosomes as a Cell-free Therapy for Myocardial Injury Following Acute Myocardial Infarction or Ischemic Reperfusion.

Exosomes, which contain miRNA, have been receiving growing attention in cardiovascular therapy because of their role in mediating cell-cell communication, autophagy, apoptosis, inflammation, and angiogenesis. Several studies have suggested that miRNA derived from exosomes can be used to detect myocardial infarctions (MI) in patients. Basic research also suggests that exosomes could serve as a potential therapeutic target for treating acute myocardial infarction. Ischemia/reperfusion (IR) injury is associated with adverse cardiac events after acute MI. We aim to review the potential benefits and mechanisms of exosomes in treating MI and IR injury.

Pathophysiology and molecular mechanism of caveolin involved in myocardial protection strategies in ischemic conditioning.

Multiple pathophysiological pathways are activated during the process of myocardial injury. Various cardioprotective strategies protect the myocardium from ischemia, infarction, and ischemia/reperfusion (I/R) injury through different targets, yet the clinical translation remains limited. Caveolae and its structure protein, caveolins, have been suggested as a bridge to transmit damage-preventing signals and mediate the protection of ultrastructure in cardiomyocytes under pathological conditions. In this review, we first briefly introduce caveolae and caveolins. Then we review the cardioprotective strategies mediated by caveolins through various pathophysiological pathways. Finally, some possible research directions are proposed to provide future experiments and clinical translation perspectives targeting caveolin based on the investigative evidence.