Short-Chain Fatty Acid Propionate Protects From Hypertensive Cardiovascular Damage.
Angiotensin II
Animals
Anti-Inflammatory Agents
/ pharmacology
Aortic Diseases
/ drug therapy
Arrhythmias, Cardiac
/ immunology
Arterial Pressure
/ drug effects
Atherosclerosis
/ drug therapy
Cardiomegaly
/ immunology
Disease Models, Animal
Hypertension
/ chemically induced
Male
Mice, Knockout, ApoE
Plaque, Atherosclerotic
Propionates
/ pharmacology
T-Lymphocytes, Regulatory
/ drug effects
Th17 Cells
/ drug effects
T-lymphocytes, regulatory
Th17 cells
angiotensin II
apolipoproteins E
fatty acids, volatile
immunology
inflammation
microbiota
Journal
Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763
Informations de publication
Date de publication:
12 03 2019
12 03 2019
Historique:
pubmed:
28
12
2018
medline:
24
12
2019
entrez:
28
12
2018
Statut:
ppublish
Résumé
Arterial hypertension and its organ sequelae show characteristics of T cell-mediated inflammatory diseases. Experimental anti-inflammatory therapies have been shown to ameliorate hypertensive end-organ damage. Recently, the CANTOS study (Canakinumab Antiinflammatory Thrombosis Outcome Study) targeting interleukin-1β demonstrated that anti-inflammatory therapy reduces cardiovascular risk. The gut microbiome plays a pivotal role in immune homeostasis and cardiovascular health. Short-chain fatty acids (SCFAs) are produced from dietary fiber by gut bacteria and affect host immune homeostasis. Here, we investigated effects of the SCFA propionate in 2 different mouse models of hypertensive cardiovascular damage. To investigate the effect of SCFAs on hypertensive cardiac damage and atherosclerosis, wild-type NMRI or apolipoprotein E knockout-deficient mice received propionate (200 mmol/L) or control in the drinking water. To induce hypertension, wild-type NMRI mice were infused with angiotensin II (1.44 mg·kg Propionate significantly attenuated cardiac hypertrophy, fibrosis, vascular dysfunction, and hypertension in both models. Susceptibility to cardiac ventricular arrhythmias was significantly reduced in propionate-treated angiotensin II-infused wild-type NMRI mice. Aortic atherosclerotic lesion area was significantly decreased in propionate-treated apolipoprotein E knockout-deficient mice. Systemic inflammation was mitigated by propionate treatment, quantified as a reduction in splenic effector memory T cell frequencies and splenic T helper 17 cells in both models, and a decrease in local cardiac immune cell infiltration in wild-type NMRI mice. Cardioprotective effects of propionate were abrogated in regulatory T cell-depleted angiotensin II-infused mice, suggesting the effect is regulatory T cell-dependent. Our data emphasize an immune-modulatory role of SCFAs and their importance for cardiovascular health. The data suggest that lifestyle modifications leading to augmented SCFA production could be a beneficial nonpharmacological preventive strategy for patients with hypertensive cardiovascular disease.
Sections du résumé
BACKGROUND
Arterial hypertension and its organ sequelae show characteristics of T cell-mediated inflammatory diseases. Experimental anti-inflammatory therapies have been shown to ameliorate hypertensive end-organ damage. Recently, the CANTOS study (Canakinumab Antiinflammatory Thrombosis Outcome Study) targeting interleukin-1β demonstrated that anti-inflammatory therapy reduces cardiovascular risk. The gut microbiome plays a pivotal role in immune homeostasis and cardiovascular health. Short-chain fatty acids (SCFAs) are produced from dietary fiber by gut bacteria and affect host immune homeostasis. Here, we investigated effects of the SCFA propionate in 2 different mouse models of hypertensive cardiovascular damage.
METHODS
To investigate the effect of SCFAs on hypertensive cardiac damage and atherosclerosis, wild-type NMRI or apolipoprotein E knockout-deficient mice received propionate (200 mmol/L) or control in the drinking water. To induce hypertension, wild-type NMRI mice were infused with angiotensin II (1.44 mg·kg
RESULTS
Propionate significantly attenuated cardiac hypertrophy, fibrosis, vascular dysfunction, and hypertension in both models. Susceptibility to cardiac ventricular arrhythmias was significantly reduced in propionate-treated angiotensin II-infused wild-type NMRI mice. Aortic atherosclerotic lesion area was significantly decreased in propionate-treated apolipoprotein E knockout-deficient mice. Systemic inflammation was mitigated by propionate treatment, quantified as a reduction in splenic effector memory T cell frequencies and splenic T helper 17 cells in both models, and a decrease in local cardiac immune cell infiltration in wild-type NMRI mice. Cardioprotective effects of propionate were abrogated in regulatory T cell-depleted angiotensin II-infused mice, suggesting the effect is regulatory T cell-dependent.
CONCLUSIONS
Our data emphasize an immune-modulatory role of SCFAs and their importance for cardiovascular health. The data suggest that lifestyle modifications leading to augmented SCFA production could be a beneficial nonpharmacological preventive strategy for patients with hypertensive cardiovascular disease.
Identifiants
pubmed: 30586752
doi: 10.1161/CIRCULATIONAHA.118.036652
pmc: PMC6416008
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Propionates
0
Angiotensin II
11128-99-7
propionic acid
JHU490RVYR
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1407-1421Références
Hypertension. 2010 Feb;55(2):500-7
pubmed: 20038749
Nat Immunol. 2013 Oct;14(10):1007-13
pubmed: 24048122
Nat Med. 2014 Feb;20(2):159-66
pubmed: 24390308
Hypertension. 2016 Aug;68(2):289-96
pubmed: 27354427
J Clin Invest. 2013 Mar;123(3):1323-34
pubmed: 23426179
Environ Microbiol. 2017 Jan;19(1):29-41
pubmed: 27928878
J Am Soc Nephrol. 2016 Mar;27(3):677-86
pubmed: 26319245
Circulation. 2009 Jun 9;119(22):2904-12
pubmed: 19470887
J Clin Invest. 2014 Oct;124(10):4204-11
pubmed: 25271725
Cell. 2016 Jun 2;165(6):1332-1345
pubmed: 27259147
Hypertension. 2012 Dec;60(6):1430-6
pubmed: 23108651
Nature. 2017 Nov 30;551(7682):585-589
pubmed: 29143823
Proc Natl Acad Sci U S A. 2013 Mar 12;110(11):4410-5
pubmed: 23401498
Nat Rev Cardiol. 2015 Apr;12(4):199-211
pubmed: 25666404
Circulation. 2018 Oct 23;138(17):e484-e594
pubmed: 30354654
Am J Physiol Renal Physiol. 2015 Jun 1;308(11):F1197-9
pubmed: 25834073
Hypertension. 2015 Jun;65(6):1331-40
pubmed: 25870193
JCI Insight. 2017 Apr 6;2(7):e92720
pubmed: 28405625
Physiol Genomics. 2016 Nov 1;48(11):826-834
pubmed: 27664183
Science. 2013 Aug 2;341(6145):569-73
pubmed: 23828891
J Am Coll Cardiol. 2015 May 12;65(18):1998-2038
pubmed: 25840655
Pflugers Arch. 2018 Apr;470(4):661-667
pubmed: 29352340
Microbiome. 2017 Feb 1;5(1):14
pubmed: 28143587
Nat Med. 2006 Feb;12(2):178-80
pubmed: 16462800
Circ Res. 2016 Apr 15;118(8):1233-43
pubmed: 26988069
Nature. 2013 Dec 19;504(7480):451-5
pubmed: 24226773
Circulation. 2006 Jan 3;113(1):51-9
pubmed: 16380549
N Engl J Med. 1987 Sep 24;317(13):787-92
pubmed: 2957590
Hypertension. 2009 Sep;54(3):619-24
pubmed: 19620507
Am J Pathol. 2002 Nov;161(5):1679-93
pubmed: 12414515
Mucosal Immunol. 2015 Jan;8(1):80-93
pubmed: 24917457
Curr Hypertens Rep. 2016 Mar;18(3):21
pubmed: 26846785
J Am Heart Assoc. 2012 Feb;1(1):27-41
pubmed: 23130116
Hypertension. 2011 Mar;57(3):469-76
pubmed: 21263125
Cardiovasc Res. 1996 Dec;32(6):1096-107
pubmed: 9015412
Arch Intern Med. 2005 Jan 24;165(2):150-6
pubmed: 15668359
Cytokine. 2010 Feb;49(2):185-93
pubmed: 19836260
Nat Commun. 2012;3:1245
pubmed: 23212374
N Engl J Med. 2017 Sep 21;377(12):1119-1131
pubmed: 28845751
J Nutr Biochem. 2008 Sep;19(9):587-93
pubmed: 18061431
Gut. 1987 Oct;28(10):1221-7
pubmed: 3678950
Arterioscler Thromb Vasc Biol. 1999 Mar;19(3):611-6
pubmed: 10073964
Cardiovasc Res. 2004 May 1;62(2):426-36
pubmed: 15094362
Immunity. 2015 Oct 20;43(4):817-29
pubmed: 26488817
Nat Immunol. 2011 Mar;12(3):204-12
pubmed: 21321594
Circulation. 2017 Mar 7;135(10):964-977
pubmed: 27927713
Hypertension. 2004 Sep;44(3):277-82
pubmed: 15302839