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Aging Healthy, or with Diabetes, is Associated with ACE2/ACE Imbalance in the Hematopoietic Stem Progenitor Cells
Author(s) -
Joshi Shrinidh,
Gomez Samuel,
DuranMendez Miguel,
QuirozOlvera Julio,
Garcia Charles,
Jarajapu Yagna PR
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.514.7
Subject(s) - progenitor cell , angiotensin converting enzyme 2 , diabetes mellitus , haematopoiesis , endocrinology , medicine , bone marrow , angiotensin converting enzyme , peripheral blood mononuclear cell , cd34 , renin–angiotensin system , enzyme , stem cell , biology , immunology , biochemistry , microbiology and biotechnology , covid-19 , blood pressure , disease , infectious disease (medical specialty) , in vitro
Bone marrow‐derived hematopoietic stem progenitor cells (HSPCs) have vasoreparative functions and are physiologically mobilized into circulation. Aging or diabetes increases risk for cardiovascular diseases and are known to be associated with impaired HSPC functions. Angiotensin converting enzyme (ACE) and ACE2 are primary enzymes of cardiovascular detrimental and protective axes of renin‐angiotensin system (RAS). Angiotensin‐(1‐7) is generated largely by degradation of Ang II by ACE2 and produces vasoprotective functions by activating Mas receptor. We have shown that Ang‐(1‐7) reverses diabetic dysfunction in murine and human HSPCs. This study tested the hypothesis that aging healthy or with diabetes is associated with imbalance in the vascular protective and detrimental axes of RAS in HSPCs. Peripheral blood samples were obtained from either male or female healthy (n=23) or diabetic (n=21), both type 1 and type 2, individuals of age ranging from 25 to 87 years. Lineage‐negative (Lin − ) or CD34 + HSPCs were enriched from mononuclear cells. ACE and ACE2 activities in the cell lysates were determined by using enzyme‐specific fluorogenic substrates. Enzyme activities are expressed as arbitrary fluorescence units that is inhibitable by the enzyme‐selective inhibitors of ACE or ACE2, captopril and MLN‐4760, respectively. ACE2/ACE activity ratios in HSPCs in different individuals are plotted against the respective ages. ACE2/ACE is negatively correlated with the age in healthy (Pearson's r=−0.88, P<0.0001) and in diabetic individuals (Pearson's r=−0.82, P<0.0001). As predicted, a negative correlation was observed with ACE2/ACE vs HbA1C (Pearson's r=−0.899, P<0.0001). These results imply that vascular protective axis of RAS is dysfunctional in HSPCs of aging individuals either healthy or diabetic, which is likely to be an underlying mechanism of the impaired reparative functions in HSPCs. Molecular or pharmacological approaches that enhance ACE2 activity or expression could be of great promise in reversing the age‐ or diabetes‐associated dysfunctions and restore cardiovascular health. Support or Funding Information National Institute of General Medical Sciences (NIGMS), and National Institute of Aging (AG056881) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .