Soluble Flt-1 links microvascular disease with heart failure in CKD

Marco, Giovana Seno Di; Kentrup, Dominik; Reuter, Stefan; Mayer, Anna B.; Golle, Lina; Tiemann, Klaus; Fobker, Manfred; Engelbertz, Christiane; Breithardt, Günter; Brand, Eva; Reinecke, Holger; Pavenstädt, Hermann; Brand, Marcus

doi:10.1007/s00395-015-0487-4

Cited by 37 publications

(53 citation statements)

References 54 publications

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“…30 Di Marco et al also revealed that exogenous administration of sFlt-1 causes heart failure by reducing heart capillary density and myocardial blood flow, with interstitial fibrosis and mitochondrial damages in rats. 8 Importantly, angiogenic factors are considered to have an important role in the process of adaptive cardiac response to pressure overload. [31][32][33] These results suggest that higher than normal levels of sFlt-1 may result in adverse effects on cardiac function by binding and sequestering angiogenic factors, leading to impaired angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Section: Suppressed Production Of Soluble Fms-like Tyrosine Kinase-1 mentioning

confidence: 99%

“…2 Recently, it has been shown that sFlt-1 is implicated in the pathogenesis of cardiovascular disease. [3][4][5][6][7][8][9][10] In a series of previous studies, 3,4,11 we demonstrated that sFlt-1 production is decreased in patients with chronic kidney disease (CKD) and in an experimental model of renal failure 3 and that decreased sFlt-1 production correlates with the development of atherosclerosis and cardiovascular events. 3,4 Furthermore, previous reports showed that the gene delivery of sFlt-1 suppresses atherosclerosis development in an animal model, 5 and the increase in sFlt-1 levels induced by atorvastatin treatment is associated with improvement of ventricular Seno et al sFlt-1 and Heart Failure 679 function in patients with acute coronary syndrome.…”

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confidence: 94%

“…35,40 Although the physiological function of sFlt-1 is probably different depending on the presence or absence of pregnancy, previous studies showed that administration of exogenous sFlt-1 in a rat model causes high blood pressure in the absence of pregnancy. 8,35 However, the clinical significance of sFlt-1 in blood pressure remains unclear. One potential limitation of our study is the measuring method of blood pressure in mice.…”

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confidence: 99%

“…7,8 In clinical settings, plasma levels of sFlt-1 are not only directly correlated with the severity of heart failure but also strongly associated with poor outcomes in patients with heart failure. 9,10 These observations provide a plausible interpretation that increased sFlt-1 production aggravates heart failure with adverse cardiac remodeling by sequestering angiogenic factors.…”

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Suppressed Production of Soluble Fms-Like Tyrosine Kinase-1 Contributes to Myocardial Remodeling and Heart Failure

et al. 2016

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Abstract-Soluble fms-like tyrosine kinase-1 (sFlt-1), an endogenous inhibitor of vascular endothelial growth factor and placental growth factor, is involved in the pathogenesis of cardiovascular disease. However, the significance of sFlt-1 in heart failure has not been fully elucidated. We found that sFlt-1 is decreased in renal failure and serves as a key molecule in atherosclerosis. In this study, we aimed to investigate the role of the decreased sFlt-1 production in heart failure, using sFlt-1 knockout mice. sFlt-1 knockout mice and wild-type mice were subjected to transverse aortic constriction and evaluated after 7 days. The sFlt-1 knockout mice had significantly higher mortality (52% versus 15%; P=0.0002) attributable to heart failure and showed greater cardiac hypertrophy (heart weight to body weight ratio, 8.95±0.45 mg/g in sFlt-1 knockout mice versus 6.60±0.32 mg/g in wild-type mice; P<0.0001) and cardiac dysfunction, which was accompanied by a significant increase in macrophage infiltration and cardiac fibrosis, than wild-type mice after transverse aortic constriction. An anti-placental growth factor-neutralizing antibody prevented pressure overload-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction. Moreover, monocyte chemoattractant protein-1 expression was significantly increased in the hypertrophied hearts of sFlt-1 knockout mice compared with wild-type mice. Monocyte chemoattractant protein-1 inhibition with neutralizing antibody ameliorated maladaptive cardiac remodeling in sFlt-1 knockout mice after transverse aortic constriction. In conclusion, decreased sFlt-1 production plays a key role in the aggravation of cardiac hypertrophy and heart failure through upregulation of monocyte chemoattractant protein-1 expression in pressure-overloaded heart. Correspondence to Yoshihiko Saito, First Department of Internal Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. E-mail saitonaramed@gmail.com Suppressed Production of Soluble Fms-Like Tyrosine Kinase-1 Contributes to MyocardialRemodeling and Heart Failure Ayako Seno, Yukiji Takeda, Masaru Matsui, Aya Okuda, Tomoya Nakano, Yasuki Nakada, Takuya Kumazawa, Hitoshi Nakagawa, Taku Nishida, Kenji Onoue, Satoshi Somekawa, Makoto Watanabe, Hiroyuki Kawata, Rika Kawakami, Hiroyuki Okura, Shiro Uemura, Yoshihiko Saito © 2016 American Heart Association, Inc. function in patients with acute coronary syndrome. 6 Therefore, it seems that insufficient sFlt-1 production is associated with adverse cardiovascular outcomes.On the contrary, several previous reports have shown that upregulation of sFlt-1 contributes to the development of heart failure, with antiangiogenesis activity by binding to VEGF. 7,8 In clinical settings, plasma levels of sFlt-1 are not only directly correlated with the severity of heart failure but also strongly associated with poor outcomes in patients with heart failure.9,10 These observations provide a plausible interpretation that increased sFlt-1 production aggravates heart failure with adverse car...

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Section: Discussionmentioning

confidence: 99%

Section: Suppressed Production Of Soluble Fms-like Tyrosine Kinase-1 mentioning

confidence: 99%

mentioning

confidence: 94%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Suppressed Production of Soluble Fms-Like Tyrosine Kinase-1 Contributes to Myocardial Remodeling and Heart Failure

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Residual alterations of cardiac and endothelial function in patients who recovered from Takotsubo cardiomyopathy

Zilberman

Zalik

Fugenfirov

et al. 2021

Clinical Cardiology

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Introduction Takotsubo cardiomyopathy (TCM) is characterized by transient left ventricle dysfunction. Hypothesis A residual cardiac and endothelial dysfunction is present in patients who recovered from TCM. Methods In this single‐center prospective study, patients with prior TCM were included and followed for 6.4 ± 1.6 years. All underwent comprehensive cardiac function assessment, including tissue Doppler imaging (TDI) and 2‐dimensional strain (2DS) echocardiography at their first visit. The number of circulating endothelial progenitor cells and levels of proangiogenic vascular endothelial growth factor (VEGF) and its receptor (VEGF‐R) were measured. All measurements were compared with healthy controls. Results Forty‐two women (age 58. ±8.6 years, LVEF 58.1 ± 6.1%) comprised the TCM group. Patients post‐TCM had significantly lower early velocities E′ (6 (5.0–8.0) vs. 9 (7.0–11.0) cm/s, p = .001) by TDI and higher E/E′ ratio (p = .002), lower LV global average longitudinal strain (LGS) (−18.9 ± 3.5% vs. −21.7 ± 2.3%, p = .002) and RV LGS (−20.1 ± 3.9% vs. −23.4 ± 2.8%, p = .003) were evident. There was a trend toward a higher VEGF‐R (p = .09) along with decreased VEGF/VEGF‐R ratio representing inadequate VEGF production. In‐hospital mortality was not reported and only two non‐cardiac deaths occurred at long‐term follow‐up. Conclusions Altered TDI and 2DS indices suggest residual biventricular myocardial injury in post‐TCM patients with the apparent LV function recovery. Inappropriate production of VEGF and VEGF‐R were observed, suggesting a possible underlying endothelial dysfunction in these patients.

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AgeR deletion decreases soluble fms-like tyrosine kinase 1 production and improves post-ischemic angiogenesis in uremic mice

Dupont¹,

Al-Rifai²,

Poitevin³

et al. 2020

Angiogenesis

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Soluble Flt-1 links microvascular disease with heart failure in CKD

Cited by 37 publications

References 54 publications

Suppressed Production of Soluble Fms-Like Tyrosine Kinase-1 Contributes to Myocardial Remodeling and Heart Failure

Suppressed Production of Soluble Fms-Like Tyrosine Kinase-1 Contributes to Myocardial Remodeling and Heart Failure

Residual alterations of cardiac and endothelial function in patients who recovered from Takotsubo cardiomyopathy

AgeR deletion decreases soluble fms-like tyrosine kinase 1 production and improves post-ischemic angiogenesis in uremic mice

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