Asia-Pacific Consensus Statement on the Management of Peripheral Artery Disease: A Report from the Asian Pacific Society of Atherosclerosis and Vascular Disease Asia-Pacific Peripheral Artery Disease Consensus Statement Project Committee.

BACKGROUND: Peripheral artery disease (PAD) is the most underdiagnosed, underestimated and undertreated of the atherosclerotic vascular diseases despite its poor prognosis. There may be racial or contextual differences in the Asia-Pacific region as to epidemiology, availability of diagnostic and therapeutic modalities, and even patient treatment response. The Asian Pacific Society of Atherosclerosis and Vascular Diseases (APSAVD) thus coordinated the development of an Asia-Pacific Consensus Statement (APCS) on the Management of PAD. OBJECTIVES: The APSAVD aimed to accomplish the following: 1) determine the applicability of the 2016 AHA/ACC guidelines on the Management of Patients with Lower Extremity Peripheral Artery Disease to the Asia-Pacific region; 2) review Asia-Pacific literature; and 3) increase the awareness of PAD. METHODOLOGY: A Steering Committee was organized to oversee development of the APCS, appoint a Technical Working Group (TWG) and Consensus Panel (CP). The TWG appraised the relevance of the 2016 AHA/ACC PAD Guideline and proposed recommendations which were reviewed by the CP using a modified Delphi technique. RESULTS: A total of 91 recommendations were generated covering history and physical examination, diagnosis, and treatment of PAD-3 new recommendations, 31 adaptations and 57 adopted statements. This Asia-Pacific Consensus Statement on the Management of PAD constitutes the first for the Asia-Pacific Region. It is intended for use by health practitioners involved in preventing, diagnosing and treating patients with PAD and ultimately the patients and their families themselves.

The role of IL-1ß in aortic aneurysm.

Interleukin-1ß (IL-1ß) is a vital cytokine that plays an important role in regulating immune responses to infectious challenges and sterile insults. In addition, two endogenous inhibitors of functional receptor binding, IL-1 receptor antagonist (IL-1Ra), complete the family. To gain biological activity, IL-1ß requires processing by the protease caspase-1 and activation of inflammasomes. Numerous clinical association studies and experimental approaches have implicated members of the IL-1 family, their receptors, or components of the processing machinery in the underlying processes of cardiovascular diseases. Here, we summarize the current state of knowledge regarding the pro-inflammatory and disease-modulating role of the IL-1 family in aneurysm. We discuss clinical evidence, signalling pathway, and mechanism of action and last, lend a perspective on currently developing therapeutic strategies involving IL-1ß in aneurysm.

The TGF-ß pathway plays a key role in aortic aneurysms.

Aortic dissection and aortic aneurysms are currently among the most high-risk cardiovascular diseases due to their rapid onset and high mortality. Although aneurysm research has been extensive, the pathogenesis remains unknown. Studies have found that the TGF-ß/Smad pathway and aneurysm formation appear linked. For example, the TGF-ß signaling pathway was significantly activated in aneurysm development and aortic dissection. Aneurysms are not, however, mitigated following knockdown of TGF-ß signaling pathway-related genes. Incidence and mortality rate of ruptured thoracic aneurysms increase with the down-regulation of the classical TGF-ß signaling pathway. In this review, we summarize recent findings and evaluate the differential role of classical and non-classical TGF-ß pathways on aortic aneurysm. It is postulated that the TGF-ß signaling pathway is necessary to maintain vascular function, but over-activation will promote aneurysms whereas over-inhibition will lead to bypass pathway over-activation and promote aneurysm occurrence.

OxLDL induces vascular endothelial cell pyroptosis through miR-125a-5p/TET2 pathway.

Pyroptosis participates in the formation and development of atherosclerosis (As) by promoting inflammatory factor release and is closely related to the stability of atherosclerotic plaque. MicroRNAs can regulate the expression of target genes at the posttranscriptional level. Previous studies have shown that miR-125a-5p increases in hyperlipidemic-hyperglycemic conditions and is involved in apoptosis, but its specific role in pyroptosis and As remains unclear. We propose that miR-125a-5p may be implicated in oxidized low-density lipoprotein (oxLDL)-induced vascular endothelial cells (VECs) pyroptosis and therefore conducted the current study. We observed that miR-125a-5p can inhibit tet methylcytosine dioxygenase 2 (TET2) expression at the posttranscription level, resulting in abnormal DNA methylation, mitochondrial dysfunction, and increased reactive oxygen species production, activated nuclear factor-κB that induces activation of inflammasome and maturation, release of proinflammatory cytokines interleukin (IL)-1ß and IL-18, and pyroptosis. Given the role of VECs in vascular physiology, oxLDL-induced VEC pyroptosis may promote the development of As. Our current study reveals a novel pathway associated with pyroptosis program regulation, which comprises miR-125a-5p and TET2 in VECs. Modulation of their expression levels may serve as a potential target for therapeutic strategies of As.