GLP-1RA therapy increases circulating vascular regenerative cell contentin people living with type 2 diabetes.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors are guideline-recommended therapies for the management of type 2 diabetes (T2D), atherosclerotic cardiovascular disease, heart failure and chronic kidney disease. We previously observed in people living with T2D and coronary artery disease that circulating vascular regenerative (VR) progenitor cell content increased following 6-month use of the SGLT2 inhibitor empagliflozin. In this post hoc sub-analysis of the ORIGINS-RCE CardioLink-13 study, we analyzed the circulating VR progenitor cell content of 92 individuals living with T2D, among whom 20 were on a GLP-1RA, 42 were on an SGLT2 inhibitor but not a GLP-1RA, and 30 were on neither of these vascular protective therapies. In the GLP-1RA group, the mean absolute count of circulating VR progenitor cells defined by high aldehyde dehydrogenase (ALDH) activity (ALDHhiSSClow) and VR progenitor cells further characterized by surface expression of the pro-angiogenic marker CD133 (ALDHhiSSClowCD133+) was higher than the group receiving neither a GLP-1RA nor an SGLT2 inhibitor (P=0.02), and comparable to that in the SGLT2 inhibitor group (P=0.25). The absolute count of pro-inflammatory, granulocyte-restricted precursor cells (ALDHhiSSChi) was significantly lower in the GLP-1RA group compared to the group on neither therapy (P=0.031). Augmented vessel repair initiated by VRcells with previously documented pro-angiogenic activity, alongside a reduction in systemic, granulocyte precursor-driven inflammation, may represent novel mechanisms responsible for the cardiovascular-metabolic benefits of GLP-1RA therapy. Prospective, randomized clinical trials are now warranted to establish the value of recovering circulating VR progenitor cell content with blood vessel regenerative functions.

GLP-1 receptor agonists and atherosclerosis protection: the vascular endothelium takes center stage.

Atherosclerotic cardiovascular disease is a chronic condition that often copresents with type 2 diabetes and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin mimetics endorsed by major professional societies for improving glycemic status and reducing atherosclerotic risk in people living with type 2 diabetes. Although the cardioprotective efficacy of GLP-1RAs and their relationship with traditional risk factors are well established, there is a paucity of publications that have summarized the potentially direct mechanisms through which GLP-1RAs mitigate atherosclerosis. This review aims to narrow this gap by providing comprehensive and in-depth mechanistic insight into the antiatherosclerotic properties of GLP-1RAs demonstrated across large outcome trials. Herein, we describe the landmark cardiovascular outcome trials that triggered widespread excitement around GLP-1RAs as a modern class of cardioprotective agents, followed by a summary of the origins of GLP-1RAs and their mechanisms of action. The effects of GLP-1RAs at each major pathophysiological milestone of atherosclerosis, as observed across clinical trials, animal models, and cell culture studies, are described in detail. Specifically, this review provides recent preclinical and clinical evidence that suggest GLP-1RAs preserve vessel health in part by preventing endothelial dysfunction, achieved primarily through the promotion of angiogenesis and inhibition of oxidative stress. These protective effects are in addition to the broad range of atherosclerotic processes GLP-1RAs target downstream of endothelial dysfunction, which include systemic inflammation, monocyte recruitment, proinflammatory macrophage and foam cell formation, vascular smooth muscle cell proliferation, and plaque development.

Vascular regenerative cells in cardiometabolic disease.

PURPOSE OF REVIEW: This review will provide an overview of the recent literature linking the pathophysiology of cardiometabolic disease with the depletion and dysfunction of circulating vascular regenerative (VR) cell content. Moreover, we provide rationale for the use of VR cells as a biomarker for cardiovascular risk and the use of pharmacological agents to improve VR cell content. RECENT FINDINGS: Recent studies demonstrate the potential of VR cells as a biomarker of cardiovascular risk and as a therapeutic target. Notably, lipid-lowering agents, antihyperglycemic therapies such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, as well as exercise and weight loss, have all been found to improve VR cell content, providing mechanistic evidence supporting a role in mitigating adverse cardiovascular outcomes in people with cardiometabolic-based disease. SUMMARY: The importance of VR cells as a biomarker in assessing cardiovascular risk is becoming increasingly apparent. This review highlights recent literature supporting the accurate use of VR cell characterization to monitor the capacity for vessel repair and novel strategies to improve vessel health. Future research is required to validate and optimize these emerging approaches.

Why We Swab: A library of stories in stem cell donation.

BACKGROUND: Stories are powerful in their ability to disseminate information in a meaningful way. We hypothesized that a stem cell donation story library optimized for social media could support the education and recruitment of committed unrelated hematopoietic stem cell donors from needed demographic groups. STUDY DESIGN AND METHODS: We developed Why We Swab, a library of stories on stem cell donation (facebook.com/WhyWeSwab; instagram.com/WhyWeSwab; twitter.com/WhyWeSwab), and evaluated its impact across social and traditional media as well as on eligible potential donors' knowledge and attitudes towards donation. RESULTS: As of December 2021, the library included 28 story arcs featuring 45 storytellers from diverse ancestral backgrounds, including 8 donor-recipient stories. Overall, the stories reached >92,000 people across social media. Notably, stories were republished by 18 print/ broadcast media outlets in Canada and by major medical organizations. A series of stories shown to 33 eligible potential donors improved mean total scores on a donation knowledge test (64% to 85%, p < 0.001), reduced mean ambivalence scale scores (3.85 to 2.70, p < 0.001), and improved participants' willingness to register as donors (45% to 73%, p < 0.005). Data are also shown demonstrating that stakeholders valued the library and that its deployment was associated with improved donor recruitment outcomes in Canada. CONCLUSION: Why We Swab is accessible and relevant to a wide audience, including stem cell donor registries and recruitment organizations seeking to improve their recruitment efforts as well as to blood and organ & tissue donation organizations who can adapt the Why We Swab model to their audiences.

Development and evaluation of a community of practice to improve stem cell donor recruitment in Canada.

Background and Objectives Communities of practice (CoPs) represent effective models to achieve quality outcomes in health care. We report the development and evaluation of a CoP to improve stem cell donor recruitment in Canada. Materials and Methods In September 2017, we invited national stakeholders in stem cell donor recruitment to participate in a Facebook group and regular e-meetings. E-meetings involved speakers and roundtable discussion on topics related to donor recruitment. The Facebook group facilitated sharing of resources. We evaluated stakeholder perspective of the CoP and the impact on recruitment outcomes. Results As of December 2020, the CoP included 382 members who published 243 posts to the Facebook group about patient/donor stories (40%), resources (27%), updates/questions (21%) and recruitment outcomes (12%). In January 2020, we surveyed 44 CoP participants; the majority felt that the Facebook group (86%) and e-meetings (59%) supported the community, and that the CoP fostered collaboration (82%), improved their donor recruitment knowledge (75%) and practice (77%) and improved their ability to recruit needed donors (64%). The launch of the CoP correlated with improved donor recruitment outcomes. In 2016-2017, CoP participants recruited 2918 registrants (46% male; 55.9% non-Caucasian) compared to 4531 registrants in 2018-2019 (52.9% male; 62.7% non-Caucasian). Members of the CoP developed innovative resources to support recruitment efforts and led national campaigns securing coverage in major media outlets. Conclusion We describe the first CoP in stem cell donor recruitment to be formally evaluated. The CoP model may be adopted by donor recruitment organisations, registries and blood banks worldwide to improve recruitment outcomes. HIGHLIGHTS: • A community of practice (CoP) in stem cell donor recruitment was valued by participants and supported efforts to improve recruitment outcomes. • The CoP model may be adopted by donor recruitment organizations, donor registries, and blood banks worldwide to improve recruitment outcomes.

Icosapent ethyl modulates circulating vascular regenerative cell content: The IPE-PREVENTION CardioLink-14 trial.

BACKGROUND: REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) showed that icosapent ethyl (IPE) reduced major adverse cardiovascular events by 25%. Since the underlying mechanisms for these benefits are not fully understood, the IPE-PREVENTION CardioLink-14 trial (ClinicalTrials.gov: NCT04562467) sought to determine if IPE regulates vascular regenerative (VR) cell content in people with mild to moderate hypertriglyceridemia. METHODS: Seventy statin-treated individuals with triglycerides ≥1.50 and <5.6 mmol/L and either atherosclerotic cardiovascular disease or type 2 diabetes with additional cardiovascular risk factors were randomized to IPE (4 g/day) or usual care. VR cells with high aldehyde dehydrogenase activity (ALDHhi) were isolated from blood collected at the baseline and 3-month visits and characterized with lineage-specific cell surface markers. The primary endpoint was the change in frequency of pro-vascular ALDHhiside scatter (SSC)lowCD133+ progenitor cells. Change in frequencies of ALDHhiSSCmid monocyte and ALDHhiSSChi granulocyte precursor subsets, reactive oxygen species production, serum biomarkers, and omega-3 levels were also evaluated. FINDINGS: Baseline characteristics, cardiovascular risk factors, and medications were balanced between the groups. Compared to usual care, IPE increased the mean frequency of ALDHhiSSClowCD133+ cells (-1.00% ± 2.45% vs. +7.79% ± 1.70%; p = 0.02), despite decreasing overall ALDHhiSSClow cell frequency. IPE assignment also reduced oxidative stress in ALDHhiSSClow progenitors and increased ALDHhiSSChi granulocyte precursor cell content. CONCLUSIONS: IPE-PREVENTION CardioLink-14 provides the first translational evidence that IPE can modulate VR cell content and suggests a novel mechanism that may underlie the cardioprotective effects observed with IPE in REDUCE-IT. FUNDING: HLS Therapeutics provided the IPE in kind and had no role in the study design, conduct, analyses, or interpretation.