Hypoxia regulate developmental coronary angiogenesis potentially through VEGF-R2- and SOX17-mediated signaling.

Background: The development of coronary vessels in embryonic mouse heart involves various progenitor populations, including sinus venosus (SV), endocardium, and proepicardium. ELA/APJ signaling is known to regulate coronary growth from the SV, whereas VEGF-A/VEGF-R2 signaling controls growth from the endocardium. Previous studies suggest hypoxia might regulate coronary growth, but its specific downstream pathways are unclear.

Elabela and Apelin regulate coronary angiogenesis in a competitive manner.

APJ, a G-protein coupled receptor, regulates coronary angiogenesis in the developing mouse heart. However, the exact mechanism by which APJ regulates coronary angiogenesis from its dual ligands, ELABELA and APELIN, is unclear. Our study show that ELABELA and APELIN both stimulate angiogenic activities such as proliferation and sprouting outgrowth in explant cultures.

Bitter melon extract suppresses metastatic breast cancer cells (MCF-7 cells) growth possibly by hindering glucose uptake.

Breast cancer is one of the most commonly diagnosed cancers among women, however the complete cure for metastatic breast cancer is lacking due to poor prognosis. There has been an increasing trend of dietary modifications including consumption of natural food for the prevention of cancer. One of the popular natural foods is bitter melon.

Hypoxia regulate developmental coronary angiogenesis potentially through VEGFR2- and SOX17-mediated signaling.

Background: Coronary vessels in embryonic mouse heart arises from multiple progenitor population including sinus venosus (SV), endocardium, and proepicardium. ELA/APJ signaling is shown to regulate coronary growth from SV pathway within the subepicardium, whereas VEGF-A/VEGF-R2 pathways is implicated to regulate coronary growth from endocardium pathway. Our previous study show hypoxia as a potential signaling cue to stimulate overall coronary growth and expansion within the myocardium.

APJ expression is lost in isolated embryonic coronary endothelial cell culture .

Coronary artery disease is one of the leading causes of death worldwide, and yet we lack the appropriate therapeutic treatments for it. Investigation into the mechanisms of coronary vessel development can provide insights into potential therapies to repair and regenerate damaged coronary arteries. Our previous study in the mouse embryo have implicated APJ, a G-protein coupled receptor that is expressed by coronary endothelial cells to be an important regulator of coronary vessel development.

APJ+ cells in the SHF contribute to the cells of aorta and pulmonary trunk through APJ signaling.

Outflow tract (OFT) develops from cardiac progenitor cells in the second heart field (SHF) domain. APJ, a G-Protein Coupled Receptor, is expressed by cardiac progenitors in the SHF. By lineage tracing APJ+SHF cells, we show that these cardiac progenitors contribute to the cells of OFT, which eventually give rise to aorta and pulmonary trunk/artery upon its morphogenesis.

Endocardium-to-coronary artery differentiation during heart development and regeneration involves sequential roles of Bmp2 and Cxcl12/Cxcr4.

Endocardial cells lining the heart lumen are coronary vessel progenitors during embryogenesis. Re-igniting this developmental process in adults could regenerate blood vessels lost during cardiac injury, but this requires additional knowledge of molecular mechanisms. Here, we use mouse genetics and scRNA-seq to identify regulators of endocardial angiogenesis and precisely assess the role of CXCL12/CXCR4 signaling.

Age-dependent decline in remyelination capacity is mediated by apelin-APJ signaling.

Age-related regeneration failure in the central nervous system can occur as a result of a decline in remyelination efficacy. The responsiveness of myelin-forming cells to signals for remyelination is affected by aging-related epigenetic modification; however, the molecular mechanism is not fully clarified. In the present study, we report that the apelin receptor (APJ) mediates remyelination efficiency with age.

In Vitro Model of Coronary Angiogenesis.

Here, we describe an in vitro culture assay to study coronary angiogenesis. Coronary vessels feed the heart muscle and are of clinical importance. Defects in these vessels represent severe health risks such as in atherosclerosis, which can lead to myocardial infarctions and heart failures in patients.

A Unique Collateral Artery Development Program Promotes Neonatal Heart Regeneration.

Collateral arteries are an uncommon vessel subtype that can provide alternate blood flow to preserve tissue following vascular occlusion. Some patients with heart disease develop collateral coronary arteries, and this correlates with increased survival. However, it is not known how these collaterals develop or how to stimulate them.

Endothelial deletion of Ino80 disrupts coronary angiogenesis and causes congenital heart disease.

During development, the formation of a mature, well-functioning heart requires transformation of the ventricular wall from a loose trabecular network into a dense compact myocardium at mid-gestation. Failure to compact is associated in humans with congenital diseases such as left ventricular non-compaction (LVNC). The mechanisms regulating myocardial compaction are however still poorly understood.

Endothelial APLNR regulates tissue fatty acid uptake and is essential for apelin's glucose-lowering effects.

Treatment of type 2 diabetes mellitus continues to pose an important clinical challenge, with most existing therapies lacking demonstrable ability to improve cardiovascular outcomes. The atheroprotective peptide apelin (APLN) enhances glucose utilization and improves insulin sensitivity. However, the mechanism of these effects remains poorly defined.

Alternative Progenitor Cells Compensate to Rebuild the Coronary Vasculature in Elabela- and Apj-Deficient Hearts.

Organogenesis during embryonic development occurs through the differentiation of progenitor cells. This process is extraordinarily accurate, but the mechanisms ensuring high fidelity are poorly understood. Coronary vessels of the mouse heart derive from at least two progenitor pools, the sinus venosus and endocardium.

Coronary Artery Development: Progenitor Cells and Differentiation Pathways.

Coronary artery disease (CAD) is the number one cause of death worldwide and involves the accumulation of plaques within the artery wall that can occlude blood flow to the heart and cause myocardial infarction. The high mortality associated with CAD makes the development of medical interventions that repair and replace diseased arteries a high priority for the cardiovascular research community. Advancements in arterial regenerative medicine could benefit from a detailed understanding of coronary artery development during embryogenesis and of how these pathways might be reignited during disease.

Isolated extraocular orbital mass: a rare presentation of sarcoidosis.

We report a case of orbital sarcoidosis in a 66 year old male who presented with one month history of right eye swelling and intermittent diplopia. MRI revealed an enhancing infiltrative soft tissue mass in the inferior aspect of the right orbit and biopsy of the mass demonstrated non-necrotizing granulomas. Chest CT scan was normal and PET scan showed no other organ involvement.

The sinus venosus contributes to coronary vasculature through VEGFC-stimulated angiogenesis.

Identifying coronary artery progenitors and their developmental pathways could inspire novel regenerative treatments for heart disease. Multiple sources of coronary vessels have been proposed, including the sinus venosus (SV), endocardium and proepicardium, but their relative contributions to the coronary circulation and the molecular mechanisms regulating their development are poorly understood. We created an ApjCreER mouse line as a lineage-tracing tool to map SV-derived vessels onto the heart and compared the resulting lineage pattern with endocardial and proepicardial contributions to the coronary circulation.

Lumican exhibits anti-angiogenic activity in a context specific manner.

A series of overexpression studies have shown that lumican suppresses angiogenesis in tumors produced from pancreatic adenocarcinoma, fibrosarcoma, and melanoma tumor cells. Despite lumican's anti-angiogenic activity, a clear correlation of differential expression of lumican in various cancers and cancer malignancy has failed to emerge. Therefore, we hypothesized that either 1.

Matrix Gla protein reinforces angiogenic resolution.

Matrix Gla Protein (MGP) is an ECM molecule commonly associated with dysfunctions of large blood vessels such as arteriosclerosis and atherosclerosis. However, the exact role of MGP in the microvasculature is not clear. Utilizing a mouse MGP knockout model we found that MGP suppresses angiogenic sprouting from mouse aorta restricts microvascular density in cardiac and skeletal muscle, and is an endogenous inhibitor of tumor angiogenesis.