Coronary artery disease (CAD) is the single leading cause of death worldwide. Advances in treatment and management have significantly improved patient outcomes. On the other hand, although mortality rates have decreased, more people are left with sequelae that require additional treatment and hospitalization. Moreover, patients with severe nonrevascularizable CAD remain with only the option of heart transplantation, which is limited by the shortage of suitable donors. In recent years, cell‐based regenerative therapy has emerged as a possible alternative treatment, with several regenerative medicinal products already in the clinical phase of development and others emerging as competitive preclinical solutions. Recent evidence indicates that pericytes, the mural cells of blood microvessels, represent a promising therapeutic candidate. Pericytes are abundant in the human body, play an active role in angiogenesis, vessel stabilization and blood flow regulation, and possess the capacity to differentiate into multiple cells of the mesenchymal lineage. Moreover, early studies suggest a robustness to hypoxic insult, making them uniquely equipped to withstand the ischemic microenvironment. This review summarizes the rationale behind pericyte‐based cell therapy and the progress that has been made toward its clinical application. We present the different sources of pericytes and the case for harvesting them from tissue leftovers of cardiovascular surgery. We also discuss the healing potential of pericytes in preclinical animal models of myocardial ischemia (MI) and current practices to upgrade the production protocol for translation to the clinic. Standardization of these procedures is of utmost importance, as lack of uniformity in cell manufacturing may influence clinical outcome. Stem Cells 2018;36:1295–1310

Homozygosity for a four-missense single-nucleotide polymorphism haplotype of the human BPIFB4 gene is enriched in long-living individuals. Delivery of this longevity-associated variant (LAV) improved revascularisation and reduced endothelial dysfunction and atherosclerosis in mice through a mechanism involving the stromal cell-derived factor-1 (SDF-1). Here, we investigated if delivery of the LAV-BPIFB4 gene may attenuate the progression of diabetic cardiomyopathy.

The cytochrome P450s (CYPs) represent a highly divergent class of enzymes involved in the oxidation of organic compounds. A subgroup of CYPs metabolize ω3-arachidonic and linoleic acids and ω6-docosahexaenoic and eicosapentaenoic polyunsaturated fatty acids (PUFAs) into a series of related biologically active mediators. Over the past 20 years, increasing evidence has emerged for a role of these PUFA-derived mediators in physiological and pathophysiological processes in the vasculature, during inflammation, and in the regulation of metabolism. With recent technological advances and increased availability of lipid mass spectroscopy, we are now starting to discern the patterns of these CYP-PUFA products in health and disease. These analyses not only are revealing the diverse spectrum of lipid nutrients regulated by CYPs, but also clearly indicate that the balance of these mediators changes with dietary intake of different PUFA classes. These findings suggest that we are only just beginning to understand all of the relevant lipid species produced by CYP pathways. Moreover, we are still a long way from understanding the nature and presence of their receptors, their tissue expression, and the pathophysiological processes they regulate. This review highlights these future issues in the context of lipid-metabolizing CYP enzymes, focusing particularly on the CYP450 family of epoxygenases and the lipid mediators they produce.