Neuropeptide Y receptor Y2 gene polymorphism interacts with plasma neuropeptide Y levels in predicting left ventricular hypertrophy in dialysis patients

Testa, Alessandra; Mallamaci, Francesca; Macrì, Roberta; Pisano, Anna; Spoto, Belinda; Malatino, Lorenzo; Stancanelli, Benedetta; Tripepi, Giovanni; Benedetto, Francesco; Zoccali, Carmine

doi:10.1097/hjh.0b013e32833bd21b

Cited by 9 publications

(11 citation statements)

References 37 publications

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“…Previous studies report that circulating NPY is substantially elevated according to the level of kidney function. 36,37 In this study, plasma NPY in AG-treated mice was lower than in untreated mice, similarly to SDF-1. Therefore, we concluded that NPY did not contribute to renal protection by AG.…”

Section: Discussionsupporting

confidence: 53%

Protection of Glucagon-Like Peptide-1 in Cisplatin-Induced Renal Injury Elucidates Gut-Kidney Connection

Katagiri¹,

Hamasaki

Doi

et al. 2013

Journal of the American Society of Nephrology

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Accumulating evidence of the beyond-glucose lowering effects of a gut-released hormone, glucagon-like peptide-1 (GLP-1), has been reported in the context of remote organ connections of the cardiovascular system. Specifically, GLP-1 appears to prevent apoptosis, and inhibition of dipeptidyl peptidase-4 (DPP-4), which cleaves GLP-1, is renoprotective in rodent ischemia-reperfusion injury models. Whether this renoprotection involves enhanced GLP-1 signaling is unclear, however, because DPP-4 cleaves other molecules as well. Thus, we investigated whether modulation of GLP-1 signaling attenuates cisplatin (CP)-induced AKI. Mice injected with 15 mg/kg CP had increased BUN and serum creatinine and CP caused remarkable pathologic renal injury, including tubular necrosis. Apoptosis was also detected in the tubular epithelial cells of CP-treated mice using immunoassays for single-stranded DNA and activated caspase-3. Treatment with a DPP-4 inhibitor, alogliptin (AG), significantly reduced CP-induced renal injury and reduced the renal mRNA expression ratios of Bax/Bcl-2 and Bim/Bcl-2. AG treatment increased the blood levels of GLP-1, but reversed the CP-induced increase in the levels of other DPP-4 substrates such as stromal cell-derived factor-1 and neuropeptide Y. Furthermore, the GLP-1 receptor agonist exendin-4 reduced CP-induced renal injury and apoptosis, and suppression of renal GLP-1 receptor expression in vivo by small interfering RNA reversed the renoprotective effects of AG. These data suggest that enhancing GLP-1 signaling ameliorates CP-induced AKI via antiapoptotic effects and that this gut-kidney axis could be a new therapeutic target in AKI.

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Section: Discussionsupporting

confidence: 53%

Protection of Glucagon-Like Peptide-1 in Cisplatin-Induced Renal Injury Elucidates Gut-Kidney Connection

Katagiri¹,

Hamasaki

Doi

et al. 2013

Journal of the American Society of Nephrology

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“…It is reported that circulating NPY is increased in patients with various diseases including diabetes, hypertension, cardiac hypertrophy, heart failure and end-stage renal disease [6][7][8][9][10][11], suggesting a close relationship between persistently high levels of NPY and these chronic diseases. Notably, plasma NPY has been considered a potential biomarker for the diagnosis of cardiovascular diseases [10,12,13]. However, the functional significance of elevated plasma NPY is not entirely clear and needs to be investigated.…”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, very few studies have been conducted to evaluate the potential effects of long-term elevations of plasma NPY on the structure and function of the heart. In vivo studies are limited to the finding that plasma levels of NPY are increased and correlated with left ventricular hypertrophy in patients with hypertension or end-stage renal disease [10,27]. There is no report on the direct effects and the associated mechanisms of sustained elevated plasma NPY on the heart in a normal animal model.…”

Section: Introductionmentioning

confidence: 99%

Long-Term Administration of Neuropeptide Y in the Subcutaneous Infusion Results in Cardiac Dysfunction and Hypertrophy in Rats

Zhang

Niu

Kang

et al. 2015

Cell Physiol Biochem

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Background/Aims: The purpose of the present study was to clarify whether chronically elevated plasma neuropeptide Y (NPY) might affect heart function and cardiac remodeling in rats. Methods: Male Wistar rats were administered NPY (85 μg for 30 days) by mini-osmotic pump subcutaneously implanted between the scapulae. Associated indices for heart function, cardiac remodeling and hypertrophy were evaluated. Results: Compared to the sham group, the baseline systolic blood pressure (SBP) in rats administered NPY was significantly increased; cardiac function was significantly decreased, as indicated by reduced ejection fraction (EF), left ventricular end-systolic pressure (LVESP), maximum change velocity of left ventricular pressure in the isovolumic contraction or relaxation period (±dp/dt_max) and increased left ventricular end-diastolic pressure (LVEDP); hematoxylin-eosin (H&E) staining detection displayed enlarged cell areas and a consistent increase in heart-to-body weight ratios (HW/BW) was observed; quantitative real time PCR (qRT-PCR) and Western blot analysis showed markedly increased expressions of β-myosin heavy chain (β-MHC), calcineurin (CaN) and phosphorylated p38 proteins, while no changes were found in the expressions of p38 total protein and the phosphorylations of JNK and ERK. Conclusion: This study reported for the first time that long-term elevated plasma concentration of NPY could induce cardiac dysfunction and cardiac hypertrophy and this phenomenon could, in part, be mediated by the Ca²⁺/CaM-dependent CaN pathway and p38 mitogen-activated protein kinase (MAPK) signal pathway in rats.

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“…Increasing evidence suggest that the level of NPY in plasma is significantly elevated in hypertrophy [10], hypertension [11] and myocardial ischemia [12]. Elevated levels of plasma NPY have also been proposed as a prognostic marker for coronary diseases [13], heart failure [14] and myocardial ischemia [15].…”

Section: Introductionmentioning

confidence: 99%

Blockage of Peripheral NPY Y1 and Y2 Receptors Modulates Barorefex Sensitivity of Diabetic Rats

Liu

Wang²,

Xie³

et al. 2013

Cell Physiol Biochem

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Background/Aims: Abnormal baroreceptor reflex sensitivity (BRS) and elevated plasma neuropeptide Y (NPY) are prevalent in diabetic patients. The present study was conducted to determine whether NPY Y1 receptor (Y1R) and NPY Y2 receptor (Y2R) contribute to the regulatin of BRS in diabetic rats. Methods: Diabetes mellitus (DM) rats with hyperlipidemia were developed by an emulsion diet enriched with fat, sucrose and fructose followed by streptozocin (STZ). Y1R and Y2R specific antagonists (BIBP 3226 and BIIE 0246) were administered by a mini-osmotic pump. Systolic blood pressure (SBP), heart rate (HR), BRS and heart functions, as well as the plasma NPY and lipid level were measured after treatment for 4 weeks. Results: Both BIBP 3226 and BIIE 0246 treatment reversed the elevated total cholesterol (TC) and low density lipoprotein (LDL-C) level, and reduced high density lipoprotein (HDL-C) level in DM rats. BIIE 0246 may attenuate the increased triglyceride (TG) level in DM rats. In addition, neither BIBP 3226 nor BIIE 0246 treatment produced significant effects on BRS, SBP or HR (P>0.05) in DM rats, even after PE and SNP challenge. However, BIBP 3226 and BIIE 0246 further impaired LVSP, LVEDP, +dp/dt_max and -dp/dt_max. Conclusion: This study provided us with the evidence that the inhibition of peripheral Y1R and Y2R did not affect impaired BRS but amplified the deterioration of the compromised cardiac function in STZ-induced DM rats with hyperlipidemia.

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Neuropeptide Y receptor Y2 gene polymorphism interacts with plasma neuropeptide Y levels in predicting left ventricular hypertrophy in dialysis patients

Cited by 9 publications

References 37 publications

Protection of Glucagon-Like Peptide-1 in Cisplatin-Induced Renal Injury Elucidates Gut-Kidney Connection

Protection of Glucagon-Like Peptide-1 in Cisplatin-Induced Renal Injury Elucidates Gut-Kidney Connection

Long-Term Administration of Neuropeptide Y in the Subcutaneous Infusion Results in Cardiac Dysfunction and Hypertrophy in Rats

Blockage of Peripheral NPY Y1 and Y2 Receptors Modulates Barorefex Sensitivity of Diabetic Rats

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