Distinct role of autophagy on angiogenesis: highlights on the effect of autophagy in endothelial lineage and progenitor cells

Hassanpour, Mehdi; Rezabakhsh, Aysa; Pezeshkian, Masoud; Rahbarghazi‬, Reza; Nouri, Mohammad

doi:10.1186/s13287-018-1060-5

Cited by 62 publications

(50 citation statements)

References 184 publications

(207 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Apoptosis is triggered in ischemic tissues in order to remove damaged or unhealthy cells, accompanied by the repair of lost tissues via the active proliferation of the intact cell components. Autophagy, on the other hand, is an adaptive response to environmental stresses including nutrient starvation due to tissue destruction or blood shortage, and it seems to be also required for the development of vascular ECs [80]. Downregulation of BAG3 could represent an increase in apoptosis but reduced autophagy [79,81], mainly in the CACtreated mice, although further studies should confirm such hypothesis.…”

Section: Discussionmentioning

confidence: 95%

Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia

et al. 2020

View full text Add to dashboard Cite

Background: Critical limb ischemia (CLI) constitutes the most aggressive form of peripheral arterial occlusive disease, characterized by the blockade of arteries supplying blood to the lower extremities, significantly diminishing oxygen and nutrient supply. CLI patients usually undergo amputation of fingers, feet, or extremities, with a high risk of mortality due to associated comorbidities. Circulating angiogenic cells (CACs), also known as early endothelial progenitor cells, constitute promising candidates for cell therapy in CLI due to their assigned vascular regenerative properties. Preclinical and clinical assays with CACs have shown promising results. A better understanding of how these cells participate in vascular regeneration would significantly help to potentiate their role in revascularization. Herein, we analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiogenesis within the ischemic tissues.

show abstract

Section: Discussionmentioning

confidence: 95%

Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Therefore, the study of multiple differentiation capacity of distinct stem cells or progenitors could enable us in concomitant promotion of angiogenesis and cardiomyogenesis [26]. More than a decade, studies have suggested that different signaling pathways, such as autophagy, are involved to commence a novel cell-fate acquisition in different cell types [27]. Due to a lack of sufficient data, we reasoned that pharmacological modulation of autophagy (either stimulation or inhibition) in bone marrow-derived CD146 + cells would modulate the differentiation capacity and further change regenerative capacity.…”

Section: Discussionmentioning

confidence: 99%

Autophagy modulation altered differentiation capacity of CD146+ cells toward endothelial cells, pericytes, and cardiomyocytes

Hassanpour

Rezaie

Darabi

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: To date, many attempts are employed to increase the regenerative potential of stem cells. In this study, we evaluated the hypothesis whether an autophagy modulation could induce/reduce CD146+ cells differentiation into mature pericyte, endothelial and cardiomyocyte lineage. Methods In this study, CD146+ cells were enriched from human bone marrow aspirates and trans-differentiated into mature EC, PC and CM after exposure to autophagy stimulator (50 µM Met)/inhibitor (15 µM HCQ). The protein levels of autophagy proteins were monitored by western blotting. NO content was measured using the Griess assay. Using real-time PCR assay and western blotting, we monitored the lineage protein and gene levels. The fatty acid change was determined by gas chromatography. Pro-inflammatory cytokine and angiocrine factors were measured by ELISA. The exosome secretion capacity was assessed by AChE activity and real-time PCR assay. Result Data revealed the modulation of autophagy factors, Beclin-1, P62 and LC3 II/I ratio in differentiating CD146+ cells after exposure to Met and HCQ (p<0.05). The inhibition of autophagy increased released NO content and decreased intracellular NO content compared to the Met-treated cells (p<0.05). Real-time PCR analysis showed that the treatment of CD146+ cells with autophagy modulators altered the expression of VE-cadherin, cTnI and α-SMA. Our data demonstrated that the stimulation of autophagy signaling in CD146+ cells with Met increased the expression of VE-cadherin, α-SMA, and cTnI compared to HCQ-treated cells (p<0.05) while western blotting revealed the protein synthesis of all lineage-specific proteins in under the stimulation and inhibition of autophagy. Fatty acid profile analysis revealed the increase of unsaturated fatty acids after exposure to HCQ (p<0.05). None statistically significant differences were found in the levels of Tie-1, Tie-2, VEGFR-1 and VEGFR-2 after autophagy modulation. The treatment of cells with HCQ increased the levels of TNF-α and IL-6 compared to the Met-treated cells. Data revealed the increase of exosome biogenesis and secretion to the supernatant in cells treated with HCQ compared to the Met groups (p<0.05).ConclusionsIn summary, autophagy modulation could be altered differentiation potency of CD146+ cells and could be novel and applicable cardiac cell therapy in the cardiac regeneration field.

show abstract

“…Therefore, the study of multiple differentiation capacity of distinct stem cells or progenitors could enable us in concomitant promotion of angiogenesis and cardiomyogenesis [27]. More than a decade, studies have suggested that different signaling pathways, such as autophagy, are involved to commence a novel cell-fate acquisition in different cell types [28]. Due to a lack of sufficient data, we reasoned that pharmacological modulation of autophagy (either stimulation or inhibition) in bone marrowderived CD146 + cells would modulate the differentiation capacity and further change regenerative capacity.…”

Section: Discussionmentioning

confidence: 99%

Autophagy modulation altered differentiation capacity of CD146+ cells toward endothelial cells, pericytes, and cardiomyocytes

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: To date, many attempts are employed to increase the regenerative potential of stem cells. In this study, we evaluated the hypothesis of whether an autophagy modulation could alter differentiation potency of CD146 + cells into mature pericyte, endothelial, and cardiomyocyte lineage. Methods: In this study, CD146 + cells were enriched from the human bone marrow aspirates and trans-differentiated into mature endothelial cells, pericytes, and cardiomyocytes after exposure to autophagy stimulator (50-μM Met)/inhibitor (15-μM HCQ). The protein levels of autophagy proteins were monitored by western blotting. NO content was measured using the Griess assay. Using real-time PCR assay and western blotting, we monitored the lineage protein and gene levels. Pro-inflammatory cytokine and angiocrine factors were measured by ELISA. The fatty acid change was determined by gas chromatography. We also measured exosome secretion capacity by measuring AChE activity and real-time PCR assay. Result: Data revealed the modulation of autophagy factors, Beclin-1, P62, and LC3 II/I ratio in differentiating CD146 + cells after exposure to Met and HCQ (p < 0.05). The inhibition of autophagy increased NO content compared to the Mettreated cells (p < 0.05). Real-time PCR analysis showed that the treatment of CD146 + cells with autophagy modulators altered the expression of VE-cadherin, cTnI, and α-SMA (p < 0.05). Met increased the expression of VE-cadherin, α-SMA, and cTnI compared to the HCQ-treated cells (p < 0.05) while western blotting revealed the protein synthesis of all lineagespecific proteins under the stimulation and inhibition of autophagy. None statistically significant differences were found in the levels of Tie-1, Tie-2, VEGFR-1, and VEGFR-2 after autophagy modulation. Fatty acid profile analysis revealed the increase of unsaturated fatty acids after exposure to HCQ (p < 0.05). The treatment of cells with HCQ increased the levels of TNF-α and IL-6 compared to the Met-treated cells. Data revealed the increase of exosome biogenesis and secretion to the supernatant in cells treated with HCQ compared to the Met groups (p < 0.05).

show abstract

Distinct role of autophagy on angiogenesis: highlights on the effect of autophagy in endothelial lineage and progenitor cells

Cited by 62 publications

References 184 publications

Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia

Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia

Autophagy modulation altered differentiation capacity of CD146+ cells toward endothelial cells, pericytes, and cardiomyocytes

Autophagy modulation altered differentiation capacity of CD146+ cells toward endothelial cells, pericytes, and cardiomyocytes

Contact Info

Product

Resources

About