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Valentina Parisi, MD, PhDDipartimento di Scienze Mediche Traslazionali
Università degli Studi di Napoli ‘Federico II
CHRONIC LOW GRADE INFLAMMATION NELL’ANZIANO:
INSUFFICIENZA CARDIACA
Heart Disease and Stroke Statistics—2013 Update A Report From the American Heart Association. Circulation (2013).
HF
PREVALENZA DELLO SCOMPENSO CARDIACOANZIANI
INFIAMMAZIONE ED INSUFFICIENZA CARDIACA
Etiologia dello scompenso Aterosclerosi Valulopatie
Storia naturale dello scompenso Rimodellamento Aritmie
INFIAMMAZIONE ED ATEROSCLEROSI
Teleb, S. Arch Cardiovasc Dis 2016
INFIAMMAZIONE E RIMODELLAMENTO
Westman PC, JACC 2016
INFIAMMAZIONE ED ARITMIE
Lazzerini PE, Eur Heart J, 2016
INFIAMMAZIONE E STENOSI AORTICA
Dweck MR, JACC 2012
INFIAMMAZIONE E TESSUTO ADIPOSO
Ghigliotti G, Inflammation 2014
Iacobellis et al. Trends in Endocrinology and Metabolism 2011
Epicardial adipose tissue
Epicardial adipose tissue
Epicardial adipose tissue
Epicardial adipose tissue
EAT volume aumenta con l’etàNakanishi K, Circ J 2015
Epicardial adipose tissue and age
In condizioni fisiologiche Risorsa energetica per il miocardio Fonte di adipochine anti-infiammatorie ed anti-aterogeniche
In condizioni patologiche
Stato infiammatorio intrinseco Produzione e secrezione di citochine proaterogeniche e proinfiammatorie Relazione con: CAD Ipertrofia LV Disfunzione diastolica Scompenso cardiaco Fibrillazione atriale
Il tessuto adiposo epicardico è il deposito di grasso viscerale cardiaco nuovo marker di rischio cardiometabolico
Iacobellis, Trends in Endocrinology and Metabolism 2011
Epicardial adipose tissue
S. Eroglu, Nutrition Metabolism & Cardiovascular Diseases 2009
Epicardial adipose tissue andCAD
Epicardial adipose tissue andCAD
In presenza di CAD aumenta l’infiltrazione macrofagica
Polarizzazzione dei macrofagi M1/M2
M1 M2
Hirata, JACC 2011
Epicardial adipose tissue andCAD
La quantità di macrfagi M1 correla con il livelli di :IL-6; TNF-alpha; MCP-1
Hirata, JACC 2011
Epicardial adipose tissue is increased in pts with calcific aortic stenosis
Parisi V et al, Int J Cardiol 2015
Epicardial adipose tissue is increased in pts with calcific aortic stenosis
Parisi V et al, Int J Cardiol 2015
Epicardial adipose tissue is increased in pts with calcific aortic stenosis
Parisi V et al, Int J Cardiol 2015
Correlazione tra spessore EAT e secrezione di mediatori
infiammatori
Table 6 . Correlation between EAT thickness and EAT inflammatory profile
Epicardial fat
Spearman p value
PDGF .728* .017
IL-1β .887** .001
IL-1ra .936** .000
IL-2 .790* .020
IL-4 .801** .005
IL-5 .954** .000
IL-6 .691* .027
IL-7 .991** .000
IL-8 .837** .010
IL-9 .911** .000
IL-10 .960** .000
IL-12 .636* .048
IL-13 .110 .762
IL-15 .538 .108
IL-17 .838** .002
Eotaxin .850** .007
FGF basic .917** .000
G-CSF .813** .004
GM-CSF .275 .441
IFN-γ .813** .004
IP-10 .881** .001
MCP-1 .711* .048
MIP-1α .813** .004
MIP-1β .869** .001
RANTES .575 .082
TNF-α .869** .001
VEGF .569 .086
Parisi V et al, Int J Cardiol 2015
Parisi V et al, Circ Res 2016
Parisi V et al, Circ Res 2016
Epicardial adipose tissue and HF
Epicardial adipose tissue and EXERCISE
Kim MK, H Appl Phtsiol, 2009
Table 4. Statins and epicardic inflammatory pattern
No Statins Statins Pvalue
PDGF, mean ± SD 86.14±27.15 107.60±183.71 0.808
IL-1b, mean ± SD 110.00±60.00 52.00±13.94 0.044
IL-1ra, mean ± SD 1313.57±297.76 787.80±233.53 0.007
IL-2, mean ± SD 65.86±16.87 29.25±17.89 0.016
IL-4, mean ± SD 5.04±2.20 3.20±1.09 0.119
IL-5, mean ± SD 3.14±0.90 1.40±0.54 0.003
IL-6, mean ± SD 89742.14±53940.50 23579.75±19599.31 0.045
IL-7, mean ± SD 5.14±1.21 3.60±1.34 0.064
IL-8, mean ± SD 190718.00±142239.80 21379.75±16088.45
0.056
IL-9, mean ± SD 17.00±1.63 9.20±6.83 0.062
IL-10, mean ± SD 166.71±94.91 57.00±32.12 0.034
IL-12, mean ± SD 90.00±33.30 43.40±14.57 0.016
IL-13, mean ± SD 26.71±19.33 63.40±75.77 0.345
IL-15, mean ± SD 369.57±93.36 387.60±122.10 0.888
IL-17, mean ± SD 188.86±39.70 78.00±45.02 0.001
Eotaxin, mean ± SD 146.14±35.33 74.00±69.69 0.127
FGF basic, mean ± SD 478.00±394.30 448.60±236.87
0.886
G-CSF, mean ± SD 43737.00±63757.60 7061.00±6144.61 0.268
GM-CSF, mean ± SD 669.57±152.09 606.4±24.75 0.319
IFN-g, mean ± SD 326.14±73.17 212.00±79.63 0.028
IP-10, mean ± SD 2098.86±2446.33 241.20±114.62 0.091
MCP-1, mean ± SD 18885.43±4311.00 6354.67±2472.38 0.002
MIP-1a, mean ± SD 385.14±304.55 32.00±9.27 0.022
MIP-1b, mean ± SD 992.71±595.30 218.80±138.80 0.013
RANTES, mean ± SD 390.71±247.08 309.00±153.92 0.530
TNF-a, mean ± SD 175.00±51.05 105.80±59.23 0.055
VEGF, mean ± SD 1336.29±584.04 661.00±336.51 0.044
Table 5. Statins and subcutaneous inflammatory pattern
No Statins Statins pvalue
PDGF, mean ± SD 40.00±46.12 38.40±19.11 0.936
IL-1b, mean ± SD 88.00±31.09 49.60±55.23 0.153
IL-1ra, mean ± SD 852.43±256.07 687.60±622.17 0.537
IL-2, mean ± SD 135.14±211.13 45.00±30.11 0.428
IL-4, mean ± SD 5.29±0.95 3.80±3.42 0.393
IL-5, mean ± SD 2.00±0.00 1.40±0.54 0.070
IL-6, mean ± SD 75990.71±75543.21 13744.40±7083.75
0.100
IL-7, mean ± SD 6.57±2.99 3.80±1.30 0.083
IL-8, mean ± SD
304411.00±332136.3
6 17001.00±15049.55
0.182
IL-9, mean ± SD 14.14±6.51 11.80±11.69 0.700
IL-10, mean ± SD 90.00±16.47 68.00±61.12 0.473
IL-12, mean ± SD 60.43±13.24 20.80±11.18 <0.0001
IL-13, mean ± SD 89.29±55.67 38.80±36.05 0.108
IL-15, mean ± SD 363.6±64.28 350.80±178.54 0.890
IL-17, mean ± SD 161.86±43.60 144.25±134.24 0.814
Eotaxin, mean ± SD 128.00±55.31 130.00±104.81 0.968
FGF basic, mean ± SD 335.86±231.68 282.6±88.99
0.639
G-CSF, mean ± SD 26069.00±45500.98 7739.20±7870.67
0.400
GM-CSF, mean ± SD 565.12±274.92 657.20±86.68 0.491
IFN-g, mean ± SD 257.29±27.83 199.80±185.60 0.529
IP-10, mean ± SD 126.14±16.97 121.60±101.32 0.926
MCP-1, mean ± SD 17820.57±6088.65 6485.80±3932.63 0.005
MIP-1a, mean ± SD 116.14±107.59 35.80±26.48 0.138
MIP-1b, mean ± SD 388.57±167.30 208.80±152.84 0.087
RANTES, mean ± SD 650.57±726.62 230.00±121.77 0.235
TNF-a, mean ± SD 135.57±22.79 130.60±136.10 0.939
VEGF, mean ± SD 701.14±350.21 278.00±88.60 0.026
EPICARDIAL SUBCOUTANEOUS
Epicardial adipose tissue and STATINS
Parisi V, unpublished data
Azione diretta delle statine sul tessuto adiposo epicardico:
Secretoma + atorvastatina
Secretoma di controllo
PROFILOINFIAMMATORIO
BIOPSIA TESSUTO ADIPOSO EPICARDICO
24h
Parisi V, unpublished data
EPICARDIAL SUBCUTANEOUS
Parisi V, unpublished data
Azione diretta delle statine sul tessuto adiposo epicardico:
Take Home Message
Infiammazione gioca un ruolo chiave nella patogenesi e nella storia naturale dell’insufficienza cardiaca
Il tessuto adiposo viscerale è fonte di mediatori infiammatori correlati a danno d’organo
Il tessuto adiposo epicardico può essere considerato un marker di rischio cardiovascolare, l’aumento del suo spessore corrisponde a più alti livelli di citokine secrete
Potenzialità di modulare la secrezione di mediatori infiammatori da parte del tessuto adiposo epicardico
Valentina Parisi, MD, PhDDipartimento di Scienze Mediche Traslazionali
Università degli Studi di Napoli ‘Federico II
CHRONIC LOW GRADE INFLAMMATION NELL’ANZIANO:
INSUFFICIENZA CARDIACA