Skip to main content
SpringerLink
Log in

High-density lipoprotein regulates angiogenesis by affecting autophagy via miRNA-181a-5p

  • Research Paper
  • Published:
Science China Life Sciences Aims and scope Submit manuscript

Abstract

We previously demonstrated that normal high-density lipoprotein (nHDL) can promote angiogenesis, whereas HDL from patients with coronary artery disease (dHDL) is dysfunctional and impairs angiogenesis. Autophagy plays a critical role in angiogenesis, and HDL regulates autophagy. However, it is unclear whether nHDL and dHDL regulate angiogenesis by affecting autophagy. Endothelial cells (ECs) were treated with nHDL and dHDL with or without an autophagy inhibitor. Autophagy, endothelial nitric oxide synthase (eNOS) expression, miRNA expression, nitric oxide (NO) production, superoxide anion (O2•−) generation, EC migration, and tube formation were evaluated. nHDL suppressed the expression of miR-181a-5p, which promotes autophagy and the expression of eNOS, resulting in NO production and the inhibition of O2•− generation, and ultimately increasing in EC migration and tube formation. dHDL showed opposite effects compared to nHDL and ultimately inhibited EC migration and tube formation. We found that autophagy-related protein 5 (ATG5) was a direct target of miR-181a-5p. ATG5 silencing or miR-181a-5p mimic inhibited nHDL-induced autophagy, eNOS expression, NO production, EC migration, tube formation, and enhanced O2•− generation, whereas overexpression of ATG5 or miR-181a-5p inhibitor reversed the above effects of dHDL. ATG5 expression and angiogenesis were decreased in the ischemic lower limbs of hypercholesterolemic low-density lipoprotein receptor null (LDLr−/−) mice when compared to C57BL/6 mice. ATG5 overexpression improved angiogenesis in ischemic hypercholesterolemic LDLr−/− mice. Taken together, nHDL was able to stimulate autophagy by suppressing miR-181a-5p, subsequently increasing eNOS expression, which generated NO and promoted angiogenesis. In contrast, dHDL inhibited angiogenesis, at least partially, by increasing miR-181a-5p expression, which decreased autophagy and eNOS expression, resulting in a decrease in NO production and an increase in O2•− generation. Our findings reveal a novel mechanism by which HDL affects angiogenesis by regulating autophagy and provide a therapeutic target for dHDL-impaired angiogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ansell, B.J., Navab, M., Hama, S., Kamranpour, N., Fonarow, G., Hough, G., Rahmani, S., Mottahedeh, R., Dave, R., Reddy, S.T., et al. (2003). Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment. Circulation 108, 2751–2756.

    Article  CAS  PubMed  Google Scholar 

  • Arakawa, S., Honda, S., Yamaguchi, H., and Shimizu, S. (2017). Molecular mechanisms and physiological roles of Atg5/Atg7-independent alternative autophagy. Proc Jpn Acad Ser B Phys Biol Sci 93, 378–385.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  • Besler, C., Heinrich, K., Rohrer, L., Doerries, C., Riwanto, M., Shih, D.M., Chroni, A., Yonekawa, K., Stein, S., Schaefer, N., et al. (2011). Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. J Clin Invest 121, 2693–2708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bogachkov, Y.Y., Chen, L., Le Master, E., Fancher, I.S., Zhao, Y., Aguilar, V., Oh, M.J., Wary, K.K., DiPietro, L.A., and Levitan, I. (2020). LDL induces cholesterol loading and inhibits endothelial proliferation and angiogenesis in Matrigels: correlation with impaired angiogenesis during wound healing. Am J Physiol Cell Physiol 318, C762–C776.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burnap, S.A., Sattler, K., Pechlaner, R., Duregotti, E., Lu, R., Theofilatos, K., Takov, K., Heusch, G., Tsimikas, S., Fernández-Hernando, C., et al. (2021). PCSK9 activity is potentiated through HDL binding. Circ Res 129, 1039–1053.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chandel, S., Manikandan, A., Mehta, N., Nathan, A.A., Tiwari, R.K., Mohapatra, S.B., Chandran, M., Jaleel, A., Manoj, N., and Dixit, M. (2021). The protein tyrosine phosphatase PTP-PEST mediates hypoxia-induced endothelial autophagy and angiogenesis via AMPK activation. J Cell Sci 134, jcs250274.

    CAS  PubMed  Google Scholar 

  • Chattopadhyay, A., Navab, M., Hough, G., Gao, F., Meriwether, D., Grijalva, V., Springstead, J.R., Palgnachari, M.N., Namiri-Kalantari, R., Su, F., et al. (2013). A novel approach to oral apoA-I mimetic therapy. J Lipid Res 54, 995–1010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, X., Yao, Y., Yuan, F., and Xie, B. (2020). Overexpression of miR-181a-5p inhibits retinal neovascularization through endocan and the ERK1/2 signaling pathway. J Cell Physiol 235, 9323–9335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gerster, R., Eloranta, J.J., Hausmann, M., Ruiz, P.A., Cosin-Roger, J., Terhalle, A., Ziegler, U., Kullak-Ublick, G.A., von Eckardstein, A., and Rogler, G. (2014). Antiinflammatory function of high-density lipoproteins via autophagy of IκB kinase. Cell Mol Gastroenterol Hepatol 1, 171–187.e1.

    Article  PubMed  PubMed Central  Google Scholar 

  • Giricz, Z., Koncsos, G., Rajtík, T., Varga, Z.V., Baranyai, T., Csonka, C., Szobi, A., Adameová, A., Gottlieb, R.A., and Ferdinandy, P. (2017). Hypercholesterolemia downregulates autophagy in the rat heart. Lipids Health Dis 16, 60.

    Article  PubMed  PubMed Central  Google Scholar 

  • Han, Y.H., Onufer, E.J., Huang, L.H., Sprung, R.W., Davidson, W.S., Czepielewski, R. S., Wohltmann, M., Sorci-Thomas, M.G., Warner, B.W., and Randolph, G.J. (2021). Enterically derived high-density lipoprotein restrains liver injury through the portal vein. Science 373, eabe6729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hassanpour, M., Rezabakhsh, A., Pezeshkian, M., Rahbarghazi, R., and Nouri, M. (2018). Distinct role of autophagy on angiogenesis: highlights on the effect of autophagy in endothelial lineage and progenitor cells. Stem Cell Res Ther 9, 305.

    Article  PubMed  PubMed Central  Google Scholar 

  • Honda, H., Hirano, T., Ueda, M., Kojima, S., Mashiba, S., Hayase, Y., Michihata, T., Shishido, K., Takahashi, K., Hosaka, N., et al. (2017). Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis. PLoS ONE 12, e0177980.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hourigan, S.T., Solly, E.L., Nankivell, V.A., Ridiandries, A., Weimann, B.M., Henriquez, R., Tepper, E.R., Zhang, J.Q.J., Tsatralis, T., Clayton, Z.E., et al. (2018). The regulation of miRNAs by reconstituted high-density lipoproteins in diabetes-impaired angiogenesis. Sci Rep 8, 13596.

    Article  PubMed  PubMed Central  ADS  Google Scholar 

  • Huang, Y., Wu, Z., Riwanto, M., Gao, S., Levison, B.S., Gu, X., Fu, X., Wagner, M.A., Besler, C., Gerstenecker, G., et al. (2013). Myeloperoxidase, paraoxonase-1, and HDL form a functional ternary complex. J Clin Invest 123, 3815–3828.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin, F., Hagemann, N., Sun, L., Wu, J., Doeppner, T.R., Dai, Y., and Hermann, D.M. (2018). High-density lipoprotein (HDL) promotes angiogenesis via S1P3-dependent VEGFR2 activation. Angiogenesis 21, 381–394.

    Article  CAS  PubMed  Google Scholar 

  • Khine, H.W., Teiber, J.F., Haley, R.W., Khera, A., Ayers, C.R., and Rohatgi, A. (2017). Association of the serum myeloperoxidase/high-density lipoprotein particle ratio and incident cardiovascular events in a multi-ethnic population: observations from the dallas heart study. Atherosclerosis 263, 156–162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kir, D., Schnettler, E., Modi, S., and Ramakrishnan, S. (2018). Regulation of angiogenesis by microRNAs in cardiovascular diseases. Angiogenesis 21, 699–710.

    Article  CAS  PubMed  Google Scholar 

  • Klionsky, D.J., Petroni, G., Amaravadi, R.K., Baehrecke, E.H., Ballabio, A., Boya, P., Bravo-San Pedro, J.M., Cadwell, K., Cecconi, F., Choi, A.M.K., et al. (2021). Autophagy in major human diseases. EMBO J 40, e108863.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuma, A., Hatano, M., Matsui, M., Yamamoto, A., Nakaya, H., Yoshimori, T., Ohsumi, Y., Tokuhisa, T., and Mizushima, N. (2004). The role of autophagy during the early neonatal starvation period. Nature 432, 1032–1036.

    Article  CAS  PubMed  ADS  Google Scholar 

  • Kundumani-Sridharan, V., Subramani, J., Owens, C., and Das, K.C. (2021). Nrg1β released in remote ischemic preconditioning improves myocardial perfusion and decreases ischemia/reperfusion injury via ErbB2-mediated rescue of endothelial nitric oxide synthase and abrogation of Trx2 autophagy. Arterioscler Thromb Vasc Biol 41, 2293–2314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lewis, G.F., and Rader, D.J. (2005). New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res 96, 1221–1232.

    Article  CAS  PubMed  Google Scholar 

  • Li, H.M., Mo, Z.W., Peng, Y.M., Li, Y., Dai, W.P., Yuan, H.Y., Chang, F.J., Wang, T.T., Wang, M., Hu, K.H., et al. (2020). Angiogenic and antiangiogenic mechanisms of high density lipoprotein from healthy subjects and coronary artery diseases patients. Redox Biol 36, 101642.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, R., Du, J., Yao, Y., Yao, G., and Wang, X. (2019). Adiponectin inhibits high glucose-induced angiogenesis via inhibiting autophagy in RF/6A cells. J Cell Physiol 234, 20566–20576.

    Article  CAS  PubMed  Google Scholar 

  • Li, Y., Kuscu, C., Banach, A., Zhang, Q., Pulkoski-Gross, A., Kim, D., Liu, J., Roth, E., Li, E., Shroyer, K.R., et al. (2015). miR-181a-5p inhibits cancer cell migration and angiogenesis via downregulation of matrix metalloproteinase-14. Cancer Res 75, 2674–2685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, Y., Lin, S., Xie, X., Zhu, H., Fan, T., and Wang, S. (2021). Highly enriched exosomal lncRNA OIP5-AS1 regulates osteosarcoma tumor angiogenesis and autophagy through miR-153 and ATG5. Am J Transl Res 13, 4211–4223.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liang, P., Jiang, B., Li, Y., Liu, Z., Zhang, P., Zhang, M., Huang, X., and Xiao, X. (2018). Autophagy promotes angiogenesis via AMPK/Akt/mTOR signaling during the recovery of heat-denatured endothelial cells. Cell Death Dis 9, 1152.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lin, L., Liu, X., Xu, J., Weng, L., Ren, J., Ge, J., and Zou, Y. (2015). High-density lipoprotein inhibits mechanical stress-induced cardiomyocyte autophagy and cardiac hypertrophy through angiotensin II type 1 receptor-mediated PI3K/Akt pathway. J Cell Mol Med 19, 1929–1938.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meng, N., Mu, X., Lv, X., Wang, L., Li, N., and Gong, Y. (2019). Autophagy represses fascaplysin-induced apoptosis and angiogenesis inhibition via ROS and p8 in vascular endothelia cells. Biomed Pharmacother 114, 108866.

    Article  CAS  PubMed  Google Scholar 

  • Menghini, R., Casagrande, V., Marino, A., Marchetti, V., Cardellini, M., Stoehr, R., Rizza, S., Martelli, E., Greco, S., Mauriello, A., et al. (2014). MiR-216a: a link between endothelial dysfunction and autophagy. Cell Death Dis 5, e1029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miki, T., Miyoshi, T., Kotani, K., Kohno, K., Asonuma, H., Sakuragi, S., Koyama, Y., Nakamura, K., and Ito, H. (2019). Decrease in oxidized high-density lipoprotein is associated with slowed progression of coronary artery calcification: subanalysis of a prospective multicenter study. Atherosclerosis 283, 1–6.

    Article  CAS  PubMed  Google Scholar 

  • Miura, S., Fujino, M., Matsuo, Y., Kawamura, A., Tanigawa, H., Nishikawa, H., and Saku, K. (2003). High density lipoprotein-induced angiogenesis requires the activation of Ras/MAP kinase in human coronary artery endothelial cells. Arterioscler Thromb Vasc Biol 23, 802–808.

    Article  CAS  PubMed  Google Scholar 

  • Navab, M., Anantharamaiah, G.M., Hama, S., Garber, D.W., Chaddha, M., Hough, G., Lallone, R., and Fogelman, A.M. (2002). Oral administration of an Apo A-I Mimetic Peptide synthesized from D-amino acids dramatically reduces atherosclerosis in mice independent of plasma cholesterol. Circulation 105, 290–292.

    Article  CAS  PubMed  Google Scholar 

  • Navab, M., Hama, S.Y., Hough, G.P., Subbanagounder, G., Reddy, S.T., and Fogelman, A.M. (2001). A cell-free assay for detecting HDL that is dysfunctional in preventing the formation of or inactivating oxidized phospholipids. J Lipid Res 42, 1308–1317.

    Article  CAS  PubMed  Google Scholar 

  • Ni, H.Z., Liu, Z., Sun, L.L., Zhou, M., Liu, C., Li, W.D., and Li, X.Q. (2019). Metformin inhibits angiogenesis of endothelial progenitor cells via miR-221-mediated p27 expression and autophagy. Future Med Chem 11, 2263–2272.

    Article  CAS  PubMed  Google Scholar 

  • Nofer, J.R., van der Giet, M., Tölle, M., Wolinska, I., von Wnuck Lipinski, K., Baba, H. A., Tietge, U.J., Gödecke, A., Ishii, I., Kleuser, B., et al. (2004). HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3. J Clin Invest 113, 569–581.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Norata, G.D., Callegari, E., Marchesi, M., Chiesa, G., Eriksson, P., and Catapano, A.L. (2005). High-density lipoproteins induce transforming growth factor-β2 expression in endothelial cells. Circulation 111, 2805–2811.

    Article  CAS  PubMed  Google Scholar 

  • O’Reilly, M., Dillon, E., Guo, W., Finucane, O., McMorrow, A., Murphy, A., Lyons, C., Jones, D., Ryan, M., Gibney, M., et al. (2016). High-density lipoprotein proteomic composition, and not efflux capacity, reflects differential modulation of reverse cholesterol transport by saturated and monounsaturated fat diets. Circulation 133, 1838–1850.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ou, J., Wang, J., Xu, H., Ou, Z., Sorci-Thomas, M.G., Jones, D.W., Signorino, P., Densmore, J.C., Kaul, S., Oldham, K.T., et al. (2005). Effects of D-4F on vasodilation and vessel wall thickness in hypercholesterolemic LDL receptor-null and LDL receptor/apolipoprotein A-I double-knockout mice on Western diet. Circ Res 97, 1190–1197.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pencheva, N., Tran, H., Buss, C., Huh, D., Drobnjak, M., Busam, K., and Tavazoie, S.F. (2012). Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis. Cell 151, 1068–1082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Primer, K.R., Psaltis, P.J., Tan, J.T.M., and Bursill, C.A. (2020). The role of high-density lipoproteins in endothelial cell metabolism and diabetes-impaired angiogenesis. Int J Mol Sci 21, 3633.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pyo, J.O., Yoo, S.M., Ahn, H.H., Nah, J., Hong, S.H., Kam, T.I., Jung, S., and Jung, Y.K. (2013). Overexpression of Atg5 in mice activates autophagy and extends lifespan. Nat Commun 4, 2300.

    Article  PubMed  ADS  Google Scholar 

  • Qin, X., Zhang, J., Wang, B., Xu, G., Yang, X., Zou, Z., and Yu, C. (2021). Ferritinophagy is involved in the zinc oxide nanoparticles-induced ferroptosis of vascular endothelial cells. Autophagy 17, 4266–4285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramakrishnan, S., Bui Nguyen, T.M., Subramanian, I.V., and Kelekar, A. (2007). Autophagy and angiogenesis inhibition. Autophagy 3, 511–514.

    Article  Google Scholar 

  • Reglero-Real, N., Pérez-Gutiérrez, L., Yoshimura, A., Rolas, L., Garrido-Mesa, J., Barkaway, A., Pickworth, C., Saleeb, R.S., Gonzalez-Nuñez, M., Austin-Williams, S. N., et al. (2021). Autophagy modulates endothelial junctions to restrain neutrophil diapedesis during inflammation. Immunity 54, 1989–2004.e9.

    Google Scholar 

  • Robichaud, S., Rasheed, A., Pietrangelo, A., Doyoung Kim, A., Boucher, D.M., Emerton, C., Vijithakumar, V., Gharibeh, L., Fairman, G., Mak, E., et al. (2022). Autophagy is differentially regulated in leukocyte and nonleukocyte foam cells during atherosclerosis. Circ Res 130, 831–847.

    Article  CAS  PubMed  Google Scholar 

  • Rohatgi, A., Khera, A., Berry, J.D., Givens, E.G., Ayers, C.R., Wedin, K.E., Neeland, I.J., Yuhanna, I.S., Rader, D.R., de Lemos, J.A., et al. (2014). HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med 371, 2383–2393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rohatgi, A., Westerterp, M., von Eckardstein, A., Remaley, A., and Rye, K.A. (2021). HDL in the 21st century: a multifunctional roadmap for future HDL research. Circulation 143, 2293–2309.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rosenson, R.S., Brewer Jr, H.B., Ansell, B.J., Barter, P., Chapman, M.J., Heinecke, J.W., Kontush, A., Tall, A.R., and Webb, N.R. (2016). Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat Rev Cardiol 13, 48–60.

    Article  CAS  PubMed  Google Scholar 

  • Schaaf, M.B., Houbaert, D., Meçe, O., and Agostinis, P. (2019). Autophagy in endothelial cells and tumor angiogenesis. Cell Death Differ 26, 665–679.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shao, B., Tang, C., Sinha, A., Mayer, P.S., Davenport, G.D., Brot, N., Oda, M.N., Zhao, X.Q., and Heinecke, J.W. (2014). Humans with atherosclerosis have impaired ABCA1 cholesterol efflux and enhanced high-density lipoprotein oxidation by myeloperoxidase. Circ Res 114, 1733–1742.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song, G.J., Kim, S.M., Park, K.H., Kim, J., Choi, I., and Cho, K.H. (2015). SR-BI mediates high density lipoprotein (HDL)-induced anti-inflammatory effect in macrophages. Biochem Biophys Res Commun 457, 112–118.

    Article  CAS  PubMed  Google Scholar 

  • Sozen, E., Yazgan, B., Tok, O.E., Demirel, T., Ercan, F., Proto, J.D., and Ozer, N.K. (2020). Cholesterol induced autophagy via IRE1/JNK pathway promotes autophagic cell death in heart tissue. Metabolism 106, 154205.

    Article  CAS  PubMed  Google Scholar 

  • Sprott, D., Poitz, D.M., Korovina, I., Ziogas, A., Phieler, J., Chatzigeorgiou, A., Mitroulis, I., Deussen, A., Chavakis, T., and Klotzsche-von Ameln, A. (2019). Endothelial-specific deficiency of ATG5 (autophagy protein 5) attenuates ischemia-related angiogenesis. Arterioscler Thromb Vasc Biol 39, 1137–1148.

    Article  CAS  PubMed  Google Scholar 

  • Sun, L.L., Xiao, L., Du, X.L., Hong, L., Li, C.L., Jiao, J., Li, W.D., and Li, X.Q. (2019). MiR-205 promotes endothelial progenitor cell angiogenesis and deep vein thrombosis recanalization and resolution by targeting PTEN to regulate Akt/autophagy pathway and MMP2 expression. J Cell Mol Med 23, 8493–8504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun, T., Yin, L., and Kuang, H. (2020). miR-181a/b-5p regulates human umbilical vein endothelial cell angiogenesis by targeting PDGFRA. Cell Biochem Funct 38, 222–230.

    Article  CAS  PubMed  Google Scholar 

  • Tabet, F., Vickers, K.C., Cuesta Torres, L.F., Wiese, C.B., Shoucri, B.M., Lambert, G., Catherinet, C., Prado-Lourenco, L., Levin, M.G., Thacker, S., et al. (2014). HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells. Nat Commun 5, 3292.

    Article  PubMed  ADS  Google Scholar 

  • Tall, A.R., Yvan-Charvet, L., Terasaka, N., Pagler, T., and Wang, N. (2008). HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis. Cell Metab 7, 365–375.

    Article  CAS  PubMed  Google Scholar 

  • Tan, J.T.M., Prosser, H.C.G., Vanags, L.Z., Monger, S.A., Ng, M.K.C., and Bursill, C.A. (2014). High-density lipoproteins augment hypoxia-induced angiogenesis via regulation of post-translational modulation of hypoxia-inducible factor 1α. FASEB J 28, 206–217.

    Article  CAS  PubMed  Google Scholar 

  • Tian, H., Li, Y., Kang, P., Wang, Z., Yue, F., Jiao, P., Yang, N., Qin, S., and Yao, S. (2019). Endoplasmic reticulum stress-dependent autophagy inhibits glycated high-density lipoprotein-induced macrophage apoptosis by inhibiting CHOP pathway. J Cell Mol Medi 23, 2954–2969.

    Article  CAS  Google Scholar 

  • Vaisar, T., Pennathur, S., Green, P.S., Gharib, S.A., Hoofnagle, A.N., Cheung, M.C., Byun, J., Vuletic, S., Kassim, S., Singh, P., et al. (2007). Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL. J Clin Invest 117, 746–756.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, S., and Peng, D. (2012). Regulation of adipocyte autophagy—the potential anti-obesity mechanism of high density lipoprotein and ApolipoproteinA-I. Lipids Health Dis 11, 131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, Y., Zheng, Y., and Li, W. (2022). Compression loading of osteoclasts attenuated microRNA-146a-5p expression, which promotes angiogenesis by targeting adiponectin. Sci China Life Sci 65, 151–166.

    Article  CAS  PubMed  Google Scholar 

  • Wu, B.J., Shrestha, S., Ong, K.L., Johns, D., Dunn, L.L., Hou, L., Barter, P.J., and Rye, K.A. (2015). Increasing HDL levels by inhibiting cholesteryl ester transfer protein activity in rabbits with hindlimb ischemia is associated with increased angiogenesis. Int J Cardiol 199, 204–212.

    Article  PubMed  Google Scholar 

  • Xu, M., and Zhang, H. (2011). Death and survival of neuronal and astrocytic cells in ischemic brain injury: a role of autophagy. Acta Pharmacol Sin 32, 1089–1099.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan, H.X., Chen, Y.T., Li, Y.Q., Wang, Y.S., Ou, Z.J., Li, Y., Gao, J.J., Deng, M.J., Song, Y.K., Fu, L., et al. (2023). Endothelial extracellular vesicles induce acute lung injury via follistatin-like protein 1. Sci China Life Sci 17, 1–15.

    Google Scholar 

  • Yang, M., Li, S., Liu, W., Li, X., He, Y., Yang, Y., Sun, K., Zhang, L., Tian, W., Duan, L., et al. (2021). The ER membrane protein complex subunit Emc3 controls angiogenesis via the FZD4/WNT signaling axis. Sci China Life Sci 64, 1868–1883.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, B., Hou, R., Zou, Z., Luo, T., Zhang, Y., Wang, L., and Wang, B. (2018). Mechanically induced autophagy is associated with ATP metabolism and cellular viability in osteocytes in vitro. Redox Biol 14, 492–498.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, C.F., Wang, H.M., Wu, A., Li, Y., and Tian, X.L. (2021a). FHA domain of AGGF1 is essential for its nucleocytoplasmic transport and angiogenesis. Sci China Life Sci 64, 1884–1894.

    Article  CAS  PubMed  ADS  Google Scholar 

  • Zhang, J., Cui, J., Zhao, F., Yang, L., Xu, X., Shi, Y., and Wei, B. (2021b). Cardioprotective effect of MLN4924 on ameliorating autophagic flux impairment in myocardial ischemia-reperfusion injury by Sirt1. Redox Biol 46, 102114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou, D.M., Sun, L.L., Zhu, J., Chen, B., Li, X.Q., and Li, W.D. (2020). miR-9 promotes angiogenesis of endothelial progenitor cell to facilitate thrombi recanalization via targeting TRPM7 through PI3K/Akt/autophagy pathway. J Cell Mol Med 24, 4624–4632.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zou, J., Fei, Q., Xiao, H., Wang, H., Liu, K., Liu, M., Zhang, H., Xiao, X., Wang, K., and Wang, N. (2019). VEGF-A promotes angiogenesis after acute myocardial infarction through increasing ROS production and enhancing ER stress-mediated autophagy. J Cell Physiol 234, 17690–17703.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

This work was supported by the National Natural Science Foundation of China (81830013, 82100424, 92268202, 81970363), the National Key Research and Development Program of China (2021YFA0805100), Guangdong Basic and Applied Basic Research Foundation (2019B1515120092), Science and Technology Planning Project of Guangzhou, China (202103000016), the Sun Yat-sen University Clinical Research 5010 Program (2014002), Program of National Key Clinical Specialties. The authors would like to thank the patients and staff at the First Affiliated Hospital of Sun Yat-sen University for their assistance throughout this study. Thanks for the support provided by the website www.figdraw.com for the graphical abstract.

Author information

Author notes

  1. Contributed equally to this work

Authors and Affiliations

  1. Division of Cardiac Surgery, Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

    Bi-Ang Kang, Hua-Ming Li, Ya-Ting Chen, Meng-Jie Deng, Yan Li, Yue-Ming Peng, Jian-Jun Gao, Zhi-Wei Mo & Jing-Song Ou

  2. National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, China

    Bi-Ang Kang, Hua-Ming Li, Ya-Ting Chen, Meng-Jie Deng, Yan Li, Yue-Ming Peng, Jian-Jun Gao, Zhi-Wei Mo, Zhi-Jun Ou & Jing-Song Ou

  3. NHC key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, China

    Bi-Ang Kang, Hua-Ming Li, Ya-Ting Chen, Meng-Jie Deng, Yan Li, Yue-Ming Peng, Jian-Jun Gao, Zhi-Wei Mo, Zhi-Jun Ou & Jing-Song Ou

  4. Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, China

    Bi-Ang Kang, Hua-Ming Li, Ya-Ting Chen, Meng-Jie Deng, Yan Li, Yue-Ming Peng, Jian-Jun Gao, Zhi-Wei Mo, Zhi-Jun Ou & Jing-Song Ou

  5. Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

    Zhi-Wei Mo

  6. Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China

    Jia-Guo Zhou

  7. Division of Hypertension and Vascular Diseases, Department of Cardiology, Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

    Zhi-Jun Ou

  8. Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China

    Jing-Song Ou

Authors
  1. Bi-Ang Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hua-Ming Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ya-Ting Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Meng-Jie Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yue-Ming Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jian-Jun Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhi-Wei Mo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jia-Guo Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Zhi-Jun Ou
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jing-Song Ou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Zhi-Jun Ou or Jing-Song Ou.

Ethics declarations

The authors declare that they have no conflict of interest. The human and animal studies were approved by the Ethics Review Board of the First Affiliated Hospital, Sun Yat-sen University, and conformed to the Helsinki Declaration of 1975 (as revised in 2008) concerning Human and Animal Rights.

Supplemental Material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kang, BA., Li, HM., Chen, YT. et al. High-density lipoprotein regulates angiogenesis by affecting autophagy via miRNA-181a-5p. Sci. China Life Sci. 67, 286–300 (2024). https://doi.org/10.1007/s11427-022-2381-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11427-022-2381-7

Keywords

Search

Navigation