Cellular Crosstalk in the Vascular Wall Microenvironment: The Role of Exosomes in Vascular Calcification.

Vascular calcification is prevalent in aging, diabetes, chronic kidney disease, cardiovascular disease, and certain genetic disorders. However, the pathogenesis of vascular calcification is not well-understood. It has been progressively recognized that vascular calcification depends on the bidirectional interactions between vascular cells and their microenvironment. Exosomes are an essential bridge to mediate crosstalk between cells and organisms, and thus they have attracted increased research attention in recent years. Accumulating evidence has indicated that exosomes play an important role in cardiovascular disease, especially in vascular calcification. In this review, we introduce vascular biology and focus on the crosstalk between the different vessel layers and how their interplay controls the process of vascular calcification.

Histone Lysine Methylation Modification and Its Role in Vascular Calcification.

Histone methylation is an epigenetic change mediated by histone methyltransferase, and has been connected to the beginning and progression of several diseases. The most common ailments that affect the elderly are cardiovascular and cerebrovascular disorders. They are the leading causes of death, and their incidence is linked to vascular calcification (VC). The key mechanism of VC is the transformation of vascular smooth muscle cells (VSMCs) into osteoblast-like phenotypes, which is a highly adjustable process involving a variety of complex pathophysiological processes, such as metabolic abnormalities, apoptosis, oxidative stress and signalling pathways. Many researchers have investigated the mechanism of VC and related targets for the prevention and treatment of cardiovascular and cerebrovascular diseases. Their findings revealed that histone lysine methylation modification may play a key role in the various stages of VC. As a result, a thorough examination of the role and mechanism of lysine methylation modification in physiological and pathological states is critical, not only for identifying specific molecular markers of VC and new therapeutic targets, but also for directing the development of new related drugs. Finally, we provide this review to discover the association between histone methylation modification and VC, as well as diverse approaches with which to investigate the pathophysiology of VC and prospective treatment possibilities.

The crosstalk between endothelial cells and vascular smooth muscle cells aggravates high phosphorus-induced arterial calcification.

Arterial calcification is highly prevalent, particularly in patients with end-stage renal disease (ESRD). The osteogenic differentiation of vascular smooth muscle cells (VSMCs) is the critical process for the development of arterial calcification. However, the detailed mechanism of VSMCs calcification remains to be elucidated. Here, we investigated the role of exosomes (Exos) derived from endothelial cells (ECs) in arterial calcification and its potential mechanisms in ESRD. Accelerated VSMCs calcification was observed when VSMCs were exposed to ECs culture media stimulated by uremic serum or high concentration of inorganic phosphate (3.5 mM Pi). and the pro-calcification effect of the ECs culture media was attenuated by exosome depletion. Exosomes derived from high concentrations of inorganic phosphate-induced ECs (ECsHPi-Exos) could be uptaken by VSMCs and promoted VSMCs calcification. Microarray analysis showed that miR-670-3p was dramatically increased in ECsHPi-Exos compared with exosomes derived from normal concentrations of inorganic phosphate (0.9 mM Pi) induced ECs (ECsNPi-Exos). Mechanistically, insulin-like growth factor 1 (IGF-1) was identified as the downstream target of miR-670-3p in regulating VSMCs calcification. Notably, ECs-specific knock-in of miR-670-3p of the 5/6 nephrectomy with a high-phosphate diet (miR-670-3pEC-KI + NTP) mice that upregulated the level of miR-670-3p in artery tissues and significantly increased artery calcification. Finally, we validated that the level of circulation of plasma exosomal miR-670-3p was much higher in patients with ESRD compared with healthy controls. Elevated levels of plasma exosomal miR-670-3p were associated with a decline in IGF-1 and more severe artery calcification in patients with ESRD. Collectively, these findings suggested that ECs-derived exosomal miR-670-3p could promote arterial calcification by targeting IGF-1, which may serve as a potential therapeutic target for arterial calcification in ESRD patients.

The Controversial Role of Irisin in Clinical Management of Coronary Heart Disease.

Irisin, a PGC1α-dependent myokine, was once believed to have beneficial effects induced by exercise. Since its first discovery of adipose browning in 2012, multiple studies have been trying to explore the metabolic functions of irisin, such as glucose and lipid metabolism. However, recently many studies with irisin concentration measuring were doubt for methodological problems, which may account for the continuous inconsistencies. New tools like recombinant irisin and gene-knockout mice are required to reconfirm the questioned functions of irisin. In this paper, we make a critical introduction to the latest researches concerning the relationship between irisin and coronary heart disease, which includes atherosclerosis, stable angina pectoris and acute coronary syndromes. These studies provided various controversial evidence of short and long-term monitoring and therapeutic effect from molecular cellular mechanisms, in vivo experiments and epidemiological investigation. But with ambiguities, irisin still has a long way to go to identify its functions in the clinical management.

Ferroptosis and Its Potential Role in Metabolic Diseases: A Curse or Revitalization?

Ferroptosis is classified as an iron-dependent form of regulated cell death (RCD) attributed to the accumulation of lipid hydroperoxides and redox imbalance. In recent years, accumulating researches have suggested that ferroptosis may play a vital role in the development of diverse metabolic diseases, for example, diabetes and its complications (e.g., diabetic nephropathy, diabetic cardiomyopathy, diabetic myocardial ischemia/reperfusion injury and atherosclerosis [AS]), metabolic bone disease and adrenal injury. However, the specific physiopathological mechanism and precise therapeutic effect is still not clear. In this review, we summarized recent advances about the development of ferroptosis, focused on its potential character as the therapeutic target in metabolic diseases, and put forward our insights on this topic, largely to offer some help to forecast further directions.