Atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality worldwide. Atherosclerosis develops over several decades and is mediated by a complex interplay of cellular mechanisms that drive a chronic inflammatory milieu and cell-to-cell interactions between endothelial cells, smooth muscle cells and macrophages that promote plaque development and progression. While there has been significant therapeutic advancement, there remains a gap where novel therapeutic approaches can complement current therapies to provide a holistic approach for treating atherosclerosis to orchestrate the regulation of complex signalling networks across multiple cell types and different stages of disease progression. MicroRNAs (miRNAs) are emerging as important post-transcriptional regulators of a suite of molecular signalling pathways and pathophysiological cellular effects. Furthermore, circulating miRNAs have emerged as a new class of disease biomarkers to better inform clinical diagnosis and provide new avenues for personalised therapies. This review focusses on recent insights into the potential role of miRNAs both as therapeutic targets in the regulation of the most influential processes that govern atherosclerosis and as clinical biomarkers that may be reflective of disease severity, highlighting the potential theranostic (therapeutic and diagnostic) properties of miRNAs in the management of cardiovascular disease.

Mammalian cardiomyocytes undergo major maturational changes in preparation for birth and postnatal life. Immature cardiomyocytes contribute to cardiac growth via proliferation and thus the heart has the capacity to regenerate. To prepare for postnatal life, structural and metabolic changes associated with increased cardiac output and function must occur. This includes exit from the cell cycle, hypertrophic growth, mitochondrial maturation and sarcomeric protein isoform switching. However, these changes come at a price: the loss of cardiac regenerative capacity such that damage to the heart in postnatal life is permanent. This is a significant barrier to the development of new treatments for cardiac repair and contributes to heart failure. The transitional period of cardiomyocyte growth is a complex and multifaceted event. In this review, we focus on studies that have investigated this critical transition period as well as novel factors that may regulate and drive this process. We also discuss the potential use of new biomarkers for the detection of myocardial infarction and, in the broader sense, cardiovascular disease. image

The cellular origins of vasa vasorum are ill-defined and may involve circulating or local progenitor cells. We previously discovered that murine aortic adventitia contains Sca-1⁺CD45⁺progenitors that produce macrophages. Here we investigated whether they are also vasculogenic. In aortas of C57BL/6 mice, Sca-1⁺CD45⁺cells were localised to adventitia and lacked surface expression of endothelial markers (<1% for CD31, CD144, TIE-2). In contrast, they did show expression of CD31, CD144, TIE-2 and VEGFR2 in atheroscleroticApoE^−/−aortas. Although Sca-1⁺CD45⁺cells from C57BL/6 aorta did not express CD31, they formed CD31⁺colonies in endothelial differentiation media and produced interconnecting vascular-like cords in Matrigel that contained both endothelial cells and a small population of macrophages, which were located at branch points. Transfer of aortic Sca-1⁺CD45⁺cells generated endothelial cells and neovesselsde novoin a hindlimb model of ischaemia and resulted in a 50% increase in perfusion compared to cell-free control. Similarly, their injection into the carotid adventitia ofApoE^−/−mice produced donor-derived adventitial and peri-adventitial microvessels after atherogenic diet, suggestive of newly formed vasa vasorum. These findings show that beyond its content of macrophage progenitors, adventitial Sca-1⁺CD45⁺cells are also vasculogenic and may be a source ofvasa vasorumduring atherogenesis.