Perivascular Adipose Tissue and Atherosclerosis
- 18 Downloads
Adipose tissue has long been identified as a key regulator of cardiovascular health, secreting a wealth of molecules, including hormones, cytokines, and gaseous messengers, which affect the cardiovascular system in both endocrine and paracrine manners. The diversity of adipose tissue biology has led to a shift in our perception of fat as an entity, highlighting the importance of regional variability. In that context, perivascular adipose tissue, a dynamic structure surrounding most vessels in the human body, and secreting a diverse range of adipocytokines and molecules, is being flagged as a distinct depot exerting crucial effects on the adjacent vascular wall and contributing to the development of atherosclerosis. At the same time, the vascular wall releases signaling molecules that diffuse into the perivascular space, modifying its texture and composition by forcing changes in perivascular fat biology. This bi-directional interplay between the vessels and perivascular fat has enabled significant translational advances, with pericoronary adipose tissue imaging emerging as a promising field in non-invasive visualization of atherosclerosis. This chapter summarizes the current knowledge on aspects of perivascular adipose tissue biology, its interplay with the vascular wall, as well as the diagnostic and prognostic value of its imaging, which aim to revolutionize cardiovascular risk prediction.
KeywordsPerivascular adipose tissue Atherosclerosis Inflammation Computed tomography imaging Attenuation Radiomics
CPK acknowledges support from the EPSRC, the Scatcherd Fund at the University of Oxford, and the A.G. Leventis Foundation.
CA is supported in part by the British Heart Foundation (FS/16/15/32047, TG/16/3/32687), the Oxford BHF Centre of Research Excellence, the Novo Nordisk Foundation (NNF15CC0018486), and Innovate UK.
CPK performed the literature review, wrote the book chapter, and prepared the figures and table. CA provided scientific direction and wrote and reviewed the book chapter.
Conflict of Interest
The CaRi-HEART technology is subject to patent applications PCT/GB2015/052359, GB20161620494.3, GB20181818049.7, GR20180100490, and GR201801005100. CA is a founder and shareholder of Caristo Diagnostics, a CT-image analysis company.
- 3.World Health Organization. Disease burden and mortality estimates. Geneva: WHO; 2018.Google Scholar
- 5.Kalbacher D, Waldeyer C, Blankenberg S, Westermann D. Beyond conventional secondary prevention in coronary artery disease—what to choose in the era of CANTOS, COMPASS, FOURIER, ODYSSEY and PEGASUS-TIMI 54? A review on contemporary literature. Ann Transl Med. 2018;6:323.CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Souilhol C, Serbanovic-Canic J, Fragiadaki M, Chico TJ, Ridger V, Roddie H, et al. Endothelial responses to shear stress in atherosclerosis: a novel role for developmental genes. Nat Rev Cardiol. 2020;17(1):52–63. https://doi.org/10.1038/s41569-019-0239-5. [Epub ahead of print].CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Ridker PM, MacFadyen JG, Thuren T, Libby P. Residual inflammatory risk associated with interleukin-18 and interleukin-6 after successful interleukin-1β inhibition with canakinumab: further rationale for the development of targeted anti-cytokine therapies for the treatment of atherothrombosis. Eur Heart J. 2019; https://doi.org/10.1093/eurheartj/ehz542. [Epub ahead of print].
- 34.Margaritis M, Antonopoulos AS, Digby J, Lee R, Reilly S, Coutinho P, et al. Interactions between vascular wall and perivascular adipose tissue reveal novel roles for adiponectin in the regulation of endothelial nitric oxide synthase function in human vessels. Circulation. 2013;127:2209–21.CrossRefPubMedPubMedCentralGoogle Scholar
- 37.Margaritis M, Sanna F, Lazaros G, Akoumianakis I, Patel S, Antonopoulos AS, et al. Predictive value of telomere length on outcome following acute myocardial infarction: evidence for contrasting effects of vascular vs. blood oxidative stress. Eur Heart J. 2017;38:3094–104.CrossRefPubMedPubMedCentralGoogle Scholar
- 43.Antonopoulos AS, Margaritis M, Coutinho P, Shirodaria C, Psarros C, Herdman L, et al. Adiponectin as a link between type 2 diabetes and vascular NADPH oxidase activity in the human arterial wall: the regulatory role of perivascular adipose tissue. Diabetes. 2015;64:2207–19.CrossRefPubMedPubMedCentralGoogle Scholar
- 49.Xie Z, Wang X, Liu X, Du H, Sun C, Shao X, et al. Adipose-derived exosomes exert proatherogenic effects by regulating macrophage foam cell formation and polarization. JAMA. 2018;7:e007442.Google Scholar
- 56.Chadderdon SM, Belcik JT, Bader L, Kirigiti MA, Peters DM, Kievit P, et al. Proinflammatory endothelial activation detected by molecular imaging in obese nonhuman primates coincides with onset of insulin resistance and progressively increases with duration of insulin resistance. Circulation. 2014;129:471–8.CrossRefPubMedPubMedCentralGoogle Scholar
- 62.Antoniades C, Kotanidis CP, Berman DS. State-of-the-art review article. Atherosclerosis affecting fat: what can we learn by imaging perivascular adipose tissue? J Cardiovasc Comput Tomogr. 2019;13(5):288–96. https://doi.org/10.1016/j.jcct.2019.03.006. [Epub ahead of print].CrossRefPubMedPubMedCentralGoogle Scholar
- 65.Antonopoulos AS, Margaritis M, Coutinho P, Digby J, Patel R, Psarros C, et al. Reciprocal effects of systemic inflammation and brain natriuretic peptide on adiponectin biosynthesis in adipose tissue of patients with ischemic heart disease. Arterioscler Thromb Vasc Biol. 2014;34:2151–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 73.Ohyama K, Matsumoto Y, Amamizu H, Uzuka H, Nishimiya K, Morosawa S, et al. Association of coronary perivascular adipose tissue inflammation and drug-eluting stent–induced coronary hyperconstricting responses in pigs. Arterioscler Thromb Vasc Biol. 2017;37:1757–64.CrossRefPubMedPubMedCentralGoogle Scholar
- 75.Iacobellis G, Ribaudo MC, Assael F, Vecci E, Tiberti C, Zappaterreno A, et al. Echocardiographic epicardial adipose tissue is related to anthropometric and clinical parameters of metabolic syndrome: a new indicator of cardiovascular risk. J Clin Endocrinol Metab. 2003;88:5163–8.CrossRefGoogle Scholar
- 76.Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, ESC Scientific Document Group, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41(3):407–77. https://doi.org/10.1093/eurheartj/ehz425. [Epub ahead of print].CrossRefPubMedPubMedCentralGoogle Scholar
- 79.Nelson AJ, Worthley MI, Psaltis PJ, Carbone A, Dundon BK, Duncan RF, et al. Validation of cardiovascular magnetic resonance assessment of pericardial adipose tissue volume. J Magn Reson Imaging. 2009;11:15.Google Scholar
- 83.Versteylen MO, Takx RAP, Joosen IAPG, Nelemans PJ, Das M, Crijns HJGM, et al. Epicardial adipose tissue volume as a predictor for coronary artery disease in diabetic, impaired fasting glucose, and non-diabetic patients presenting with chest pain. Eur Heart J Cardiovasc Imaging. 2012;13:517–23.CrossRefPubMedPubMedCentralGoogle Scholar
- 86.Tanami Y, Jinzaki M, Kishi S, Matheson M, Vavere AL, Rochitte CE, et al. Lack of association between epicardial fat volume and extent of coronary artery calcification, severity of coronary artery disease, or presence of myocardial perfusion abnormalities in a diverse, symptomatic patient population: results from the CORE320 multicenter study. Circ Cardiovasc Imaging. 2015;8:e002676.CrossRefPubMedPubMedCentralGoogle Scholar
- 87.Franssens BT, Nathoe HM, Leiner T, van der Graaf Y, Visseren FL, group Ss. Relation between cardiovascular disease risk factors and epicardial adipose tissue density on cardiac computed tomography in patients at high risk of cardiovascular events. Eur Heart J Cardiovasc Imaging. 2017;24:660–70.Google Scholar
- 88.Mazurek T, Kobylecka M, Zielenkiewicz M, Kurek A, Kochman J, Filipiak KJ, et al. PET/CT evaluation of 18F-FDG uptake in pericoronary adipose tissue in patients with stable coronary artery disease: independent predictor of atherosclerotic lesions’ formation? J Nucl Cardiol. 2017;24:1075–84.CrossRefPubMedPubMedCentralGoogle Scholar
- 92.Antoniades C, Antonopoulos AS, Deanfield J. Imaging residual inflammatory cardiovascular risk. Eur Heart J. 2019; https://doi.org/10.1093/eurheartj/ehz474. [Epub ahead of print].
- 93.Oikonomou EK, Marwan M, Desai MY, Mancio J, Alashi A, Hutt Centeno E, et al. Non-invasive detection of coronary inflammation using computed tomography and prediction of residual cardiovascular risk (the CRISP CT study): a post-hoc analysis of prospective outcome data. Lancet. 2018;392:929–39.CrossRefPubMedPubMedCentralGoogle Scholar
- 94.Leipsic J, Abbara S, Achenbach S, Cury R, Earls JP, Mancini GJ, et al. SCCT guidelines for the interpretation and reporting of coronary CT angiography: a report of the society of cardiovascular computed tomography guidelines committee. J Cardiovasc Comput Tomogr. 2014;8:342–58.CrossRefPubMedPubMedCentralGoogle Scholar
- 95.Goeller M, Achenbach S, Cadet S, Kwan AC, Commandeur F, Slomka PJ, et al. Pericoronary adipose tissue computed tomography attenuation and high-risk plaque characteristics in acute coronary syndrome compared with stable coronary artery disease. JAMA Cardiol. 2018;3:858–63.CrossRefPubMedPubMedCentralGoogle Scholar
- 99.Elnabawi YA, Oikonomou EK, Dey AK, Mancio J, Rodante JA, Aksentijevich M, et al. Association of biologic therapy with coronary inflammation in patients with psoriasis as assessed by perivascular fat attenuation index. JAMA Cardiol. 2019; https://doi.org/10.1001/jamacardio.2019.2589. [Epub ahead of print].
- 102.Oikonomou EK, Williams MC, Kotanidis CP, Desai MY, Marwan M, Antonopoulos AS, et al. A novel machine learning-derived radiotranscriptomic signature of perivascular fat improves cardiac risk prediction using coronary CT angiography. Eur Heart J. 2019;40:3529–43.CrossRefPubMedPubMedCentralGoogle Scholar
- 104.Kolossváry M, Karády J, Szilveszter B, Kitslaar P, Hoffmann U, Merkely B, et al. Radiomic features are superior to conventional quantitative computed tomographic metrics to identify coronary plaques with napkin-ring sign. Circ Cardiovasc Imaging. 2017;10:e006843.CrossRefPubMedPubMedCentralGoogle Scholar