Cellular and Molecular Life Sciences

, Volume 76, Issue 4, pp 777–789 | Cite as

Developmental and functional characteristics of the thoracic aorta perivascular adipocyte

  • Maoqing Ye
  • Cheng-Chao RuanEmail author
  • Mengxia Fu
  • Lian Xu
  • Dongrui Chen
  • Minsheng Zhu
  • Dingliang Zhu
  • Pingjin Gao
Original Article


Thoracic aorta perivascular adipose tissue (T-PVAT) has critical roles in regulating vascular homeostasis. However, the developmental characteristics and cellular lineage of adipocyte in the T-PVAT remain unclear. We show that T-PVAT contains three long strip-shaped fat depots, anterior T-PVAT (A-T-PVAT), left lateral T-PVAT (LL-T-PVAT), and right lateral T-PVAT (RL-T-PVAT). A-T-PVAT displays a distinct transcriptional profile and developmental origin compared to the two lateral T-PVATs (L-T-PVAT). Lineage tracing studies indicate that A-T-PVAT adipocytes are primarily derived from SM22α+ progenitors, whereas L-T-PVAT contains both SM22α+ and Myf5+ cells. We also show that L-T-PVAT contains more UCP1+ brown adipocytes than A-T-PVAT, and L-T-PVAT exerts a greater relaxing effect on aorta than A-T-PVAT. Angiotensin II-infused hypertensive mice display greater macrophage infiltration into A-T-PVAT than L-T-PVAT. These combined results indicate that L-T-PVAT has a distinct development from A-T-PVAT with different cellular lineage, and suggest that L-T-PVAT and A-T-PVAT have different physiological and pathological functions.


Thoracic aorta perivascular adipocyte Development Lineage tracing SM22α Myf5 



This work was funded by grants from the National Natural Science Foundation of China (91539202, 81570221, 81770495, 91739303, 81200067), Natural Science Foundation of Shanghai (17ZR1423800), Science and Technology Commission of Shanghai Municipality (18140903402), and Shanghai Municipal Commission of Health and Family Planning (2017YQ076, 201540222).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

18_2018_2970_MOESM1_ESM.docx (14.1 mb)
Supplementary material 1 (DOCX 14476 kb)


  1. 1.
    Galassi A, Reynolds K, He J (2006) Metabolic syndrome and risk of cardiovascular disease: a meta-analysis. Am J Med 119:812–819Google Scholar
  2. 2.
    Almabrouk TA, Ewart MA, Salt IP, Kennedy S (2014) Perivascular fat, AMP-activated protein kinase and vascular diseases. Br J Pharmacol 171:595–617Google Scholar
  3. 3.
    Karastergiou K, Fried SK (2013) Multiple adipose depots increase cardiovascular risk via local and systemic effects. Curr Atherosclerosis Rep 15:361Google Scholar
  4. 4.
    Majesky MW, Dong XR, Hoglund V, Mahoney WM Jr, Daum G (2011) The adventitia: a dynamic interface containing resident progenitor cells. Arterioscler Thromb Vasc Biol 31:1530–1539Google Scholar
  5. 5.
    Withers SB, Bussey CE, Saxton SN, Melrose HM, Watkins AE, Heagerty AM (2014) Mechanisms of adiponectin-associated perivascular function in vascular disease. Arterioscler Thromb Vasc Biol 34:1637–1642Google Scholar
  6. 6.
    Aghamohammadzadeh R, Heagerty AM (2012) Obesity-related hypertension: epidemiology, pathophysiology, treatments, and the contribution of perivascular adipose tissue. Ann Med 44(Suppl 1):S74–S84Google Scholar
  7. 7.
    Bussey CE, Withers SB, Aldous RG, Edwards G, Heagerty AM (2016) Obesity-related perivascular adipose tissue damage is reversed by sustained weight loss in the rat. Arterioscler Thromb Vasc Biol 36:1377–1385Google Scholar
  8. 8.
    Friederich-Persson M, Nguyen Dinh Cat A, Persson P, Montezano AC, Touyz RM (2017) Brown adipose tissue regulates small artery function through NADPH oxidase 4-derived hydrogen peroxide and redox-sensitive protein kinase G-1alpha. Arterioscler Thromb Vasc Biol 37:455–465Google Scholar
  9. 9.
    Gollasch M (2017) Adipose-vascular coupling and potential therapeutics. Annu Rev Pharmacol Toxicol 57:417–436Google Scholar
  10. 10.
    Bays HE (2011) Adiposopathy is “sick fat” a cardiovascular disease? J Am Coll Cardiol 57:2461–2473Google Scholar
  11. 11.
    Cinti S (2011) Between brown and white: novel aspects of adipocyte differentiation. Ann Med 43:104–115Google Scholar
  12. 12.
    Hepler C, Vishvanath L, Gupta RK (2017) Sorting out adipocyte precursors and their role in physiology and disease. Genes Dev 31:127–140Google Scholar
  13. 13.
    Berry R, Rodeheffer MS (2013) Characterization of the adipocyte cellular lineage in vivo. Nat Cell Biol 15:302–308Google Scholar
  14. 14.
    Rodeheffer MS, Birsoy K, Friedman JM (2008) Identification of white adipocyte progenitor cells in vivo. Cell 135:240–249Google Scholar
  15. 15.
    Tang W, Zeve D, Suh JM, Bosnakovski D, Kyba M, Hammer RE, Tallquist MD, Graff JM (2008) White fat progenitor cells reside in the adipose vasculature. Science (New York, N.Y.) 322:583–586Google Scholar
  16. 16.
    Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scime A, Devarakonda S, Conroe HM, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR, Spiegelman BM (2008) PRDM16 controls a brown fat/skeletal muscle switch. Nature 454:961–967Google Scholar
  17. 17.
    Sanchez-Gurmaches J, Guertin DA (2014) Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed. Nature Commun 5:4099Google Scholar
  18. 18.
    Chang L, Villacorta L, Li R, Hamblin M, Xu W, Dou C, Zhang J, Wu J, Zeng R, Chen YE (2012) Loss of perivascular adipose tissue on peroxisome proliferator-activated receptor-gamma deletion in smooth muscle cells impairs intravascular thermoregulation and enhances atherosclerosis. Circulation 126:1067–1078Google Scholar
  19. 19.
    Kokkinopoulos I, Wong MM, Potter CMF, Xie Y, Yu B, Warren DT, Nowak WN, Le Bras A, Ni Z, Zhou C, Ruan X, Karamariti E, Hu Y, Zhang L, Xu Q (2017) Adventitial SCA-1(+) progenitor cell gene sequencing reveals the mechanisms of cell migration in response to hyperlipidemia. Stem cell Rep 9:681–696Google Scholar
  20. 20.
    Brown NK, Zhou Z, Zhang J, Zeng R, Wu J, Eitzman DT, Chen YE, Chang L (2014) Perivascular adipose tissue in vascular function and disease: a review of current research and animal models. Arterioscler Thromb Vasc Biol 34:1621–1630Google Scholar
  21. 21.
    Chang L, Xiong W, Zhao X, Fan Y, Guo Y, Garcia-Barrio M, Zhang J, Jiang Z, Lin JD, Chen YE (2018) Bmal1 in perivascular adipose tissue regulates resting phase blood pressure through transcriptional regulation of angiotensinogen. CirculationGoogle Scholar
  22. 22.
    Ruan CC, Zhu DL, Chen QZ, Chen J, Guo SJ, Li XD, Gao PJ (2010) Perivascular adipose tissue-derived complement 3 is required for adventitial fibroblast functions and adventitial remodeling in deoxycorticosterone acetate-salt hypertensive rats. Arterioscler Thromb Vasc Biol 30:2568–2574Google Scholar
  23. 23.
    Saxton SN, Ryding KE, Aldous RG, Withers SB, Ohanian J, Heagerty AM (2018) Role of sympathetic nerves and adipocyte catecholamine uptake in the vasorelaxant function of perivascular adipose tissue. Arterioscler Thromb Vasc BiolGoogle Scholar
  24. 24.
    Britton KA, Pedley A, Massaro JM, Corsini EM, Murabito JM, Hoffmann U, Fox CS (2012) Prevalence, distribution, and risk factor correlates of high thoracic periaortic fat in the Framingham Heart Study. J Am Heart Assoc 1:e004200Google Scholar
  25. 25.
    Ye M, Zhang Q, Xu X, Zhang Q, Ge Y, Geng P, Yan J, Luo L, Sun Y, Liang X (2016) Loss of JAM-C leads to impaired esophageal innervations and megaesophagus in mice. Dis Esophagus 29:864–871Google Scholar
  26. 26.
    Feil S, Fehrenbacher B, Lukowski R, Essmann F, Schulze-Osthoff K, Schaller M, Feil R (2014) Transdifferentiation of vascular smooth muscle cells to macrophage-like cells during atherogenesis. Circ Res 115:662–667Google Scholar
  27. 27.
    Ye M, Coldren C, Liang X, Mattina T, Goldmuntz E, Benson DW, Ivy D, Perryman MB, Garrett-Sinha LA, Grossfeld P (2010) Deletion of ETS-1, a gene in the Jacobsen syndrome critical region, causes ventricular septal defects and abnormal ventricular morphology in mice. Hum Mol Genet 19:648–656Google Scholar
  28. 28.
    Chen X, An X, Chen D, Ye M, Shen W, Han W, Zhang Y, Gao P (2016) Chronic exercise training improved aortic endothelial and mitochondrial function via an AMPKalpha2-dependent manner. Front Physiol 7:631Google Scholar
  29. 29.
    Sheng LJ, Ruan CC, Ma Y, Chen DR, Kong LR, Zhu DL, Gao PJ (2016) Beta3 adrenergic receptor is involved in vascular injury in deoxycorticosterone acetate-salt hypertensive mice. FEBS Lett 590:769–778Google Scholar
  30. 30.
    Ruan CC, Ge Q, Li Y, Li XD, Chen DR, Ji KD, Wu YJ, Sheng LJ, Yan C, Zhu DL, Gao PJ (2015) Complement-mediated macrophage polarization in perivascular adipose tissue contributes to vascular injury in deoxycorticosterone acetate-salt mice. Arterioscler Thromb Vasc Biol 35:598–606Google Scholar
  31. 31.
    Zhang Z, Turer E, Li X, Zhan X, Choi M, Tang M, Press A, Smith SR, Divoux A, Moresco EM, Beutler B (2016) Insulin resistance and diabetes caused by genetic or diet-induced KBTBD2 deficiency in mice. Proc Natl Acad Sci USA 113:E6418–E6426Google Scholar
  32. 32.
    Zhang ZB, Ruan CC, Lin JR, Xu L, Chen XH, Du YN, Fu MX, Kong LR, Zhu DL, Gao PJ (2018) Perivascular adipose tissue-derived PDGF-D contributes to aortic aneurysm formation during obesity. Diabetes 67:1549–1560Google Scholar
  33. 33.
    Tran KV, Gealekman O, Frontini A, Zingaretti MC, Morroni M, Giordano A, Smorlesi A, Perugini J, De Matteis R, Sbarbati A, Corvera S, Cinti S (2012) The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells. Cell Metab 15:222–229Google Scholar
  34. 34.
    Sowa Y, Imura T, Numajiri T, Takeda K, Mabuchi Y, Matsuzaki Y, Nishino K (2013) Adipose stromal cells contain phenotypically distinct adipogenic progenitors derived from neural crest. PLoS One 8:e84206Google Scholar
  35. 35.
    Chang L, Garcia-Barrio MT, Chen YE (2017) Brown adipose tissue, not just a heater. Arterioscler Thromb Vasc Biol 37:389–391Google Scholar
  36. 36.
    Aldiss P, Davies G, Woods R, Budge H, Sacks HS, Symonds ME (2017) ‘Browning’ the cardiac and peri-vascular adipose tissues to modulate cardiovascular risk. Int J Cardiol 228:265–274Google Scholar
  37. 37.
    Scheideler M, Herzig S, Georgiadi A (2017) Endocrine and autocrine/paracrine modulators of brown adipose tissue mass and activity as novel therapeutic strategies against obesity and type 2 diabetes. Hormon Mol Biol Clin Investig 31Google Scholar
  38. 38.
    Giralt M, Cereijo R, Villarroya F (2016) Adipokines and the endocrine role of adipose tissues. Handb Exp Pharmacol 233:265–282Google Scholar
  39. 39.
    Billon N, Dani C (2012) Developmental origins of the adipocyte lineage: new insights from genetics and genomics studies. Stem Cell Rev 8:55–66Google Scholar
  40. 40.
    Zieger K, Weiner J, Kunath A, Gericke M, Krause K, Kern M, Stumvoll M, Kloting N, Bluher M, Heiker JT (2018) Ablation of kallikrein 7 (KLK7) in adipose tissue ameliorates metabolic consequences of high fat diet-induced obesity by counteracting adipose tissue inflammation in vivo. CMLS 75:727–742Google Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension, Ruijin Hospital and Shanghai Institute of HypertensionShanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.Key Laboratory of Stem Cell Biology, Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina
  3. 3.State Key Laboratory of Pharmaceutical Biotechnology and Model Animal Research Center and MOE Key Laboratory of Model Animal for Disease StudyNanjing UniversityNanjingChina

Personalised recommendations