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