The role of telomerase reverse transcriptase in the mitochondrial protective functions of Angiotensin-(1-7) in diabetic CD34 cells.

Angiotensin (Ang)-(1-7) stimulates vasoprotective functions of diabetic (DB) CD34 hematopoietic stem/progenitor cells partly by decreasing reactive oxygen species (ROS), increasing nitric oxide (NO) levels and decreasing TGFβ1 secretion. Telomerase reverse transcriptase (TERT) translocates to mitochondria and regulates ROS generation. Alternative splicing of TERT results in variants α-, β- and α-β-TERT, which may oppose functions of full-length (FL) TERT.

Integrin β1 is a key determinant of the expression of angiotensin-converting enzyme 2 (ACE2) in the kidney epithelial cells.

The expression of the angiotensin-converting enzyme 2 (ACE2) is altered in multiple chronic kidney diseases like hypertension and renal fibrosis, where the signaling from the basal membrane proteins is critical for the development and progression of the various pathologies. Integrins are heterodimeric cell surface receptors that have important roles in the progression of these chronic kidney diseases by altering various cell signaling pathways in response to changes in the basement membrane proteins. It is unclear whether integrin or integrin-mediated signaling affects the ACE2 expression in the kidney.

Blood flow restriction exercise stimulates mobilization of hematopoietic stem/progenitor cells and increases the circulating ACE2 levels in healthy adults.

Adult CD34 hematopoietic stem/progenitor cells (HSPC) in the systemic circulation are bone marrow-derived and have the propensity of maintaining cardiovascular health. Activation of angiotensin-converting enzyme-2 (ACE2)-angiotensin-(1-7)-Mas receptor pathway, the vascular protective axis of the renin-angiotensin system (RAS), stimulates vasculogenic functions of HSPCs. In a previous study, exposure to hypoxia increased the expressions of ACE2 and Mas, and stimulated ACE2 shedding.

Diabetic pre-programming of myelopoiesis impairs tissue repair.

Bone marrow-derived monocyte-macrophages promote healing of injured tissue cooperatively with vasculogenic hematopoietic stem/progenitor cells. However, diabetes dysregulates hematopoiesis and attenuates bone marrow-derived tissue-reparative responses. In a recent issue of The Journal of Pathology, Barman et al extensively characterized myelopoietic responses in bone marrow following skin wounding in a type 2 model of diabetes.

Hypoxic regulation of angiotensin-converting enzyme 2 and Mas receptor in human CD34 cells.

CD34 hematopoietic stem/progenitor cells (HSPCs) are vasculogenic and hypoxia is a strong stimulus for the vasoreparative functions of these cells. Angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7)/Mas receptor (MasR) pathway stimulates vasoprotective functions of CD34 cells. This study tested if ACE2 and MasR are involved in the hypoxic stimulation of CD34 cells.

Angiotensin converting enzyme versus angiotensin converting enzyme-2 selectivity of MLN-4760 and DX600 in human and murine bone marrow-derived cells.

Angiotensin-converting enzymes, ACE and ACE2, are key members of renin angiotensin system. Activation of ACE2/Ang-(1-7) pathway enhances cardiovascular protective functions of bone marrow-derived stem/progenitor cells. The current study evaluated the selectivity of ACE2 inhibitors, MLN-4760 and DX-600, and ACE and ACE2 activities in human (hu) and murine (mu) bone marrow cells.