TY - JOUR
T1 - Immunometabolic mechanisms of heart failure with preserved ejection fraction
AU - Schiattarella, Gabriele G.
AU - Alcaide, Pilar
AU - Condorelli, Gianluigi
AU - Gillette, Thomas G.
AU - Heymans, Stephane
AU - Jones, Elizabeth A.V.
AU - Kallikourdis, Marinos
AU - Lichtman, Andrew
AU - Marelli-Berg, Federica
AU - Shah, Sanjiv J.
AU - Thorp, Edward B.
AU - Hill, Joseph A.
N1 - Funding Information:
This work was supported by grants from the DZHK (German Centre for Cardiovascular Research) to G.G.S.; the Deutsche Forschungsgemeinschaft (German Research Foundation; SFB-1470-A02) to G.G.S.; IMI2-CARDIATEAM (no. 821508) and the Netherlands Cardiovascular Research Initiative, Dutch Cardiovascular Alliance CVON2016-Early HFPEF, 2015-10, CVON She-PREDICTS, no. 2017-21 (to S.H.); US National Institutes of Health (HL144477 to P.A., HL122309 to E.B.T., HL160273, HL107577, HL127028, HL140731, HL149423 to S.J.S. and HL126012, HL128215, HL120732, HL147933 and HL155765 to J.A.H.) and the American Heart Association (19TPA34910006 to J.A.H.). We regret that we were unable to recognize all pertinent research in this field and contributions from all investigators owing to journal space limitations. All figures were created with BioRender.com licensed to G.G.S.
Publisher Copyright:
© 2022, Springer Nature Limited.
PY - 2022/3
Y1 - 2022/3
N2 - Heart failure with preserved ejection fraction (HFpEF) is increasing in prevalence worldwide, already accounting for at least half of all cases of heart failure. As most patients with HFpEF are obese with metabolic syndrome, metabolic stress has been implicated in syndrome pathogenesis. Recently, compelling evidence for bidirectional cross-talk between metabolic stress and chronic inflammation has emerged, and alterations in systemic and cardiac immune responses have been shown to participate in HFpEF pathophysiology. Indeed, based on both preclinical and clinical evidence, comorbidity-driven systemic inflammation, coupled with metabolic stress is held to participate in HFpEF pathogenesis. As metabolic alterations impact immune function(s) in HFpEF, major changes in immune cell metabolism are also recognized in HFpEF and in HFpEF-predisposing conditions. Both arms of immunity—innate and adaptive—are implicated in the cardiomyocyte response in HFpEF. Indeed, we submit that cross-talk among adipose tissue, the immune system and the heart represents a critical component of HFpEF pathobiology. Here, we review recent evidence in support of immunometabolic mechanisms as drivers of HFpEF pathogenesis, discuss pivotal biological mechanisms underlying the syndrome, and highlight questions requiring additional inquiry.
AB - Heart failure with preserved ejection fraction (HFpEF) is increasing in prevalence worldwide, already accounting for at least half of all cases of heart failure. As most patients with HFpEF are obese with metabolic syndrome, metabolic stress has been implicated in syndrome pathogenesis. Recently, compelling evidence for bidirectional cross-talk between metabolic stress and chronic inflammation has emerged, and alterations in systemic and cardiac immune responses have been shown to participate in HFpEF pathophysiology. Indeed, based on both preclinical and clinical evidence, comorbidity-driven systemic inflammation, coupled with metabolic stress is held to participate in HFpEF pathogenesis. As metabolic alterations impact immune function(s) in HFpEF, major changes in immune cell metabolism are also recognized in HFpEF and in HFpEF-predisposing conditions. Both arms of immunity—innate and adaptive—are implicated in the cardiomyocyte response in HFpEF. Indeed, we submit that cross-talk among adipose tissue, the immune system and the heart represents a critical component of HFpEF pathobiology. Here, we review recent evidence in support of immunometabolic mechanisms as drivers of HFpEF pathogenesis, discuss pivotal biological mechanisms underlying the syndrome, and highlight questions requiring additional inquiry.
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U2 - 10.1038/s44161-022-00032-w
DO - 10.1038/s44161-022-00032-w
M3 - Review article
C2 - 35755006
AN - SCOPUS:85129190198
SN - 2731-0590
VL - 1
SP - 211
EP - 222
JO - Nature Cardiovascular Research
JF - Nature Cardiovascular Research
IS - 3
ER -