Role of Canagliflozin on function of CD34+ve endothelial progenitor cells (EPC) in patients with type 2 diabetes

Nandula, Seshagiri Rao; Kundu, Nabanita; Awal, Hassan; Břicháček, Beda; Fakhri, Mona; Aimalla, Nikhila; Elzarki, Adrian; Amdur, Richard L.; Sen, Sabyasachi

doi:10.1186/s12933-021-01235-4

Cited by 34 publications

(23 citation statements)

References 51 publications

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“…In our study we decided to use adult stem cells such as hematopoietic progenitor cells (CD34 +) as our primary outcome measure [14]. Our laboratory group has used hematopoietic cells as a cell-based diagnostic and prognostic biomarker in multiple scenarios and have evaluated ECD evaluation modalities such as arterial stiffness measures [15], flow mediated dilatation and podocyte inflammatory markers [16][17][18][19]. This is a cross-sectional observational study examining patients with HIV and a history of taking either INSTI or NNRTI regimens for at least one year.…”

Section: Methodsmentioning

confidence: 99%

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Cardiovascular disease (CVD) risk assessment of HIV medication regimens using hematopoietic CD34+ progenitor cells

et al. 2022

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Background To determine the effects of integrase inhibitor (INSTI) in comparison with non-INSTI-based regimens such as non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based regimens on cardiovascular disease (CVD) risk in HIV+ patients without overt history of CVD or diabetes, with normal CD4:CD8 count. For CVD risk assessment we primarily used hematopoietic CD34+ progenitor cells, as a biomarker. Methods Nineteen male subjects, ages 32–61 years with BMI 21.0–36.0, were enrolled. This was a single time point, cross-sectional, observational study. Subjects were enrolled under 2 groups (either on INSTI-based regimen with 13 subjects or NNRTI (non-INSTI)-based regimens with 6 subjects) who were taking stable doses of HAART. The medication regimens were a combination of one NRTI (typically tenofovir–emtricitabine) plus one INSTI or NNRTI. Our outcome measures were focused on cardiovascular and endothelial cell function and systemic inflammation. Our primary outcome measures were peripheral blood-derived hematopoietic progenitor cell number (CD34 and CD133 positive), CD34+ cell function and gene expression studies. Our secondary outcomes were arterial stiffness measures and serum-based markers of inflammation. Results A significant increase in percentage number of progenitor cells, CD133+ cells (p = 0.004), was noted along with an increase of double progenitor mark positive CD133+/CD34+ progenitor cell population being observed in INSTI group as compared to NNRTI group, by flow cytometry. mRNA gene expression for antioxidant gene catalase was noted along with a trend toward a decrease in gene expression of inflammatory marker IL6 (p = 0.06) being observed in CD34+ from INSTI group vs NNRTI group. The plasma IL-6 and CRP levels did not change significantly between the groups. Neutrophil–Lymphocyte ratio (NLR), an important marker of inflammation, was noted to be lower in INSTI group. A mean fasting glucose level was also lower in the INSTI group compared to NNRTI group (p = 0.03). Interestingly, urine microalbumin levels were higher in the INSTI group compared to NNRTI group (p = 0.08), while eGFR levels were significantly lower in the INSTI group (p = 0.002). The arterial stiffness measures did not show statistically significant differences between the two groups. Conclusion We conclude that the INSTI regimen may provide a better CVD risk profile compared to NNRTI-based HAART regimen; however, the increased albuminuria along with lower eGFR, noted in INSTI group, is of concern. Because of the small size, these results would need replication in additional studies before changing clinical practice. Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03782142?cond=Hiv&spons=Sabyasachi+sen&cntry=US&state=US%3ADC&city=Washington&draw=2&rank=1. ClinicalTrials.gov Identifier: NCT03782142.

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Section: Methodsmentioning

confidence: 99%

“…CD34+ gene expression analysis was performed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) as previously described (16). CD34+ cell total mRNA was extracted and purified using the RNeasy Minikit (Qiagen, Germany).…”

Section: Cellular and Clinical Assessments Cd34+ Endothelial Progenit...mentioning

confidence: 99%

Cardiovascular disease (CVD) risk assessment of HIV medication regimens using hematopoietic CD34+ progenitor cells

et al. 2022

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“…In our study we decided to use adult stem cells such as hematopoietic progenitor cells (CD34+) as our primary outcome measure [12]. Our laboratory group has used hematopoietic cells as a cell based diagnostic and prognostic biomarker in multiple scenarios and have evaluated ECD evaluation modalities such as arterial stiffness measures [13], ow mediated dilatation and podocyte in ammatory markers [14][15][16][17]. This is a cross-sectional observational study examining patients with HIV and a history of taking either INSTI or NNRTI regimens for at least one year.…”

Section: Methodsmentioning

confidence: 99%

Cardiovascular Disease (CVD) Risk Assessment of HIV Medication Regimens using hematopoietic CD34+ progenitor cells

Elzarki

Nandula

Awal

et al. 2022

Preprint

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Background To determine the effects of integrase inhibitor (INSTI) in comparison to non INSTI based regimens such as non-nucleoside reverse transcriptase inhibitors (NNRTIs) based regimens on cardiovascular disease (CVD) risk in HIV+ patients without overt history of CVD or diabetes, with normal CD4:CD8 count. For CVD risk assessment we primarily used hematopoietic CD34+ progenitor cells, as a biomarker.Methods19 male subjects ages 32-61 years with BMI 21.0- 36.0, were enrolled. This was a single time point, cross-sectional, observational study. Subjects were enrolled under 2 groups (either on INSTI based regimen with 13 subjects or NNRTI (non-INSTI) based regimens with 6 subjects) who were taking stable doses of HAART. The medication regimens were a combination of one NRTI (typically tenofovir-emtricitabine) plus one INSTI or NNRTI. Our outcome measures were focused on cardiovascular and endothelial cell function and systemic inflammation. Our primary outcome measures were peripheral blood derived hematopoietic progenitor cell number (CD34 and CD133 positive), CD34+ cell function and gene expression studies. Our secondary outcomes were arterial stiffness measures and serum-based markers of inflammation. ResultsA significant increase in percentage number of progenitor cells, CD133+ cells (P=0.004) was noted along with an increase of double progenitor mark positive CD133+/CD34+ progenitor cell population was observed in INSTI group as compared to NNRTI group, by flow-cytometry. mRNA gene expression for antioxidant gene catalase was noted along with a trend towards a decrease in gene expression of inflammatory marker IL6 (p=0.06) was observed in CD34+ from INSTI group vs NNRTI group. The plasma IL-6 and CRP levels did not change significantly between the groups. Neutrophil-Lymphocyte ratio (NLR), an important marker of inflammation, was noted to be lower in INSTI group. A mean fasting glucose level was also lower in the INSTI group compared to NNRTI group (p=0.03). Interestingly, Urine- Microalbumin levels were higher in the INSTI group compared to NNRTI group (p=0.08), while eGFR levels were lower in the INSTI group (p=0.002). The arterial stiffness measures did not show statistically significant differences between the two groups. ConclusionWe conclude that the INSTI regimen may provide a better CVD risk profile compared to NNRTI based HAART regimen; however the increased albuminuria along with lower eGFR, noted in INSTI group is of concern. Because of the small size, these results would need replication in additional studies before changing clinical practice.Clinical Trial Registration https://clinicaltrials.gov/ct2/show/NCT03782142?cond=Hiv&spons=Sabyasachi+sen&cntry=US&state=US%3ADC&city=Washington&draw=2&rank=1ClinicalTrials.gov Identifier: NCT03782142

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“…However, treatment of T2DM patients with dapagliflozin or empagliflozin for 12 weeks does not significantly increase CSCs or EPGs in these patients [96]. Similarly, a pilot study found that short-term treatment with canagliflozin fails to elevate EPGs in diabetic individuals, but did improve EPG migratory function in a manner that paralleled a rise in eNOS expression, suggesting a possible involvement of EPGs in the repair process [97]. Intriguingly, a recent report found that dapagliflozin enhances endothelial repair of injured carotid arteries in STZ-treated diabetic mice by restoring the mobilization and trafficking of CD49d+ granulocytes to sites of vascular damage [98].…”

Section: Sglt2 Inhibitors Regulate Vascular Repair and Angiogenesismentioning

confidence: 98%

Effects of Sodium-Glucose Co-Transporter 2 Inhibitors on Vascular Cell Function and Arterial Remodeling

Durante

Behnammanesh

Peyton

2021

IJMS

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Cardiovascular disease is the leading cause of morbidity and mortality in diabetes. Recent clinical studies indicate that sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in patients with diabetes. The mechanism underlying the beneficial effect of SGLT2 inhibitors is not completely clear but may involve direct actions on vascular cells. SGLT2 inhibitors increase the bioavailability of endothelium-derived nitric oxide and thereby restore endothelium-dependent vasodilation in diabetes. In addition, SGLT2 inhibitors favorably regulate the proliferation, migration, differentiation, survival, and senescence of endothelial cells (ECs). Moreover, they exert potent antioxidant and anti-inflammatory effects in ECs. SGLT2 inhibitors also inhibit the contraction of vascular smooth muscle cells and block the proliferation and migration of these cells. Furthermore, studies demonstrate that SGLT2 inhibitors prevent postangioplasty restenosis, maladaptive remodeling of the vasculature in pulmonary arterial hypertension, the formation of abdominal aortic aneurysms, and the acceleration of arterial stiffness in diabetes. However, the role of SGLT2 in mediating the vascular actions of these drugs remains to be established as important off-target effects of SGLT2 inhibitors have been identified. Future studies distinguishing drug- versus class-specific effects may optimize the selection of specific SGLT2 inhibitors in patients with distinct cardiovascular pathologies.

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Role of Canagliflozin on function of CD34+ve endothelial progenitor cells (EPC) in patients with type 2 diabetes

Cited by 34 publications

References 51 publications

Cardiovascular disease (CVD) risk assessment of HIV medication regimens using hematopoietic CD34+ progenitor cells

Cardiovascular disease (CVD) risk assessment of HIV medication regimens using hematopoietic CD34+ progenitor cells

Cardiovascular Disease (CVD) Risk Assessment of HIV Medication Regimens using hematopoietic CD34+ progenitor cells

Effects of Sodium-Glucose Co-Transporter 2 Inhibitors on Vascular Cell Function and Arterial Remodeling

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