Association of increased parathyroid hormone with neuroendocrine activation and endothelial dysfunction in elderly men with heart failure

Loncar, Goran; Božić, Biljana; Dimković, Siniša; Prodanović, Nenad; Radojičić, Zoran; Cvorovic, Vojkan; Putniković, Biljana; Popović, Vera

doi:10.1007/bf03347080

Cited by 34 publications

(28 citation statements)

References 44 publications

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“…Recently, parathyroid hormone (PTH), which acts to increase calcium concentration by activating the parathyroid hormone receptor (PTHR), has been implicated in myocardial hypertrophy (27). Elevated PTH has been reported in patients with chronic heart failure (25) with an acceleration of a decompensation of the left ventricle, evidenced by reduced fractional shortening and posterior wall thickness, observed in PTH-treated mice (7). In this study, males consuming ethanol demonstrated an increase in PTH 2 receptor.…”

Section: Discussionmentioning

confidence: 59%

Functional proteomic analysis reveals sex-dependent differences in structural and energy-producing myocardial proteins in rat model of alcoholic cardiomyopathy

Fogle

Hollenbeak²,

Stanley

et al. 2011

Physiological Genomics

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Fogle RL, Hollenbeak CS, Stanley BA, Vary TC, Kimball SR, Lynch CJ. Functional proteomic analysis reveals sexdependent differences in structural and energy-producing myocardial proteins in rat model of alcoholic cardiomyopathy. Physiol Genomics 43: 346 -356, 2011. First published January 18, 2011 doi:10.1152/physiolgenomics.00203.2010.-Long-term ethanol exposure leads to a sexually dimorphic response in both the susceptibility to cardiac pathology (protective effect of the female heart) and the expression of selected myocardial proteins. The purpose of the present study was to use proteomics to examine the effect of chronic alcohol consumption on a broader array of cardiac proteins and how these were affected between the sexes. Male and female rats were maintained for 18 wk on a 40% ethanol-containing diet in which alcohol was provided in drinking water and agar blocks. Differences in the content of specific cardiac proteins in isopycnic centrifugal fractions were determined using mass spectrometry on iTRAQlabeled tryptic fragments. A random effects model of meta-analysis was developed to combine the results from multiple iTRAQ experiments. Analysis of a network of proteins involved in cardiovascular system development and function showed that troponins were oppositely regulated by alcohol exposure in females (upregulated) vs. males (downregulated), and this effect was validated by Western blot analysis. Pathway analysis also revealed that alcohol-consuming males showed increased expression of proteins involved in various steps of oxidative phosphorylation including complexes I, III, IV, and V, whereas females showed no change or decreased content. One implication from these findings is that females may be protected from the toxic effects of alcohol due to their ability to maintain contractile function, maintain efficiency of force generation, and minimize oxidative stress. However, the alcohol-induced insult may lead to increased production of reactive oxygen species and structural abnormalities in male myocardium. iTRAQ; mass spectrometry; meta-analysis; random effects ALCOHOL ABUSE REMAINS ONE of the most common forms of drug abuse among both sexes in the United States. Although the risk of cardiovascular diseases is reduced with moderate alcohol consumption, potential consequences of excessive and chronic alcohol abuse, defined as Ͼ80 g of alcohol per day for longer than 5 yr, include heart dysfunction and heart failure (47). This quantity and frequency of ethanol consumption are sufficient to induce alcoholic heart muscle disease (AHMD) and, in approximately one-third of the cases, contributes to the development of a dilated cardiomyopathy (DCM: 48,50). AHMD is rarely the result of short-term ethanol intake but is more commonly observed in patients who consume excessive amounts of alcohol for prolonged periods (48, 50). This disease is clinically characterized by adverse alterations in both the structure and function of the myocardium, including ventricular dilation, thinning of the ventricular wall, and m...

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Section: Discussionmentioning

confidence: 59%

Functional proteomic analysis reveals sex-dependent differences in structural and energy-producing myocardial proteins in rat model of alcoholic cardiomyopathy

Fogle

Hollenbeak²,

Stanley

et al. 2011

Physiological Genomics

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“…Fourth, PTH is associated with cardiovascular risk factors in the general population 29,73,102,103. Increased PTH levels are associated with hypertension,31,104–109 CAD,34,73,102 left ventricular hypertrophy,110,111 cardiac arrhythmias,112 heart failure,30,33,110,113–116 and insulin sensitivity,117 as well as cardiovascular and all-cause mortality in patients with87,118,119 and without chronic kidney disease 29,32,43,70,78,79,120–122…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular diseases in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links

Fisher¹,

Srikusalanukul²,

Davis³

et al. 2013

CIA

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BackgroundConsiderable controversy exists regarding the contribution of mineral/bone metabolism abnormalities to the association between cardiovascular diseases (CVDs) and osteoporotic fractures.Aims and methodsTo determine the relationships between mineral/bone metabolism biomarkers and CVD in 746 older patients with hip fracture, clinical data were recorded and serum concentrations of parathyroid hormone (PTH), 25-hydroxyvitamin D, calcium, phosphate, magnesium, troponin I, parameters of bone turnover, and renal, liver, and thyroid functions were measured.ResultsCVDs were diagnosed in 472 (63.3%) patients. Vitamin D deficiency was similarly prevalent in patients with (78.0%) and without (82.1%) CVD. The CVD group had significantly higher mean PTH concentrations (7.6 vs 6.0 pmol/L, P < 0.001), a higher prevalence of secondary hyperparathyroidism (SPTH) (PTH > 6.8 pmol/L, 43.0% vs 23.3%, P < 0.001), and excess bone resorption (urinary deoxypyridinoline corrected by creatinine [DPD/Cr] > 7.5 nmol/μmol, 87.9% vs 74.8%, P < 0.001). In multivariate regression analysis, SHPT (odds ratio [OR] 2.6, P = 0.007) and high DPD/Cr (OR 2.8, P = 0.016) were independent indictors of CVD. Compared to those with both PTH and DPD/Cr in the normal range, multivariate-adjusted ORs for the presence of CVD were 17.3 (P = 0.004) in subjects with SHPT and 9.7 (P < 0.001) in patients with high DPD/Cr. CVD was an independent predicator of SHPT (OR 2.8, P = 0.007) and excess DPD/Cr (OR 2.5, P = 0.031). CVD was predictive of postoperative myocardial injury, while SHPT was also an independent predictor of prolonged hospital stay and in-hospital death.ConclusionSHPT and excess bone resorption are independent pathophysiological mediators underlying the bidirectional associations between CVD and hip fracture, and therefore are important diagnostic and therapeutic targets.

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“…PTH may therefore serve a role in the pathophysiology of cardiovascular disease (13). A series of previous studies (14,15) have suggested that PTH may directly induce endothelial dysfunction and contribute to VC. However, the underlying mechanisms of this remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Parathyroid hormone promotes osteoblastic differentiation of endothelial cells via the extracellular signal‑regulated protein kinase 1/2 and nuclear factor‑κB signaling pathways

Cheng

Ling³

et al. 2017

Exp Ther Med

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Abstract. Vascular calcification (VC) occurs in patients with chronic kidney disease (CKD) and contributes to cardiovascular dysfunction and mortality. Parathyroid hormone (PTH) is a crucial regulator of VC. High PTH serum levels constitute as a major risk factor for patients with CKD. However, the effect and mechanism of PTH on osteoblastic differentiation in endothelial cells have not been fully elucidated. In the present study, the role of PTH in VC was investigated using an in vitro calcification model. Endothelial cells were stimulated with PTH in the femto-to picomolar range. As determined by western blot analysis and ELISA, osteoblastic differentiation, as indicated by the BMP2 marker, occurred with maximum effect at 1x10 -10 mmol/l PTH. The results indicate that PTH promotes osteoblastic differentiation of endothelial cells, as demonstrated by the increased expression of bone morphogenetic protein (BMP) 2 and BMP4. In addition, western blot analysis revealed that PTH activated the extracellular signal-regulated protein kinase (Erk)1/2 and nuclear factor (NF)-κB signaling pathways. However, reverse transcription-quantitative polymerase chain reaction demonstrated that inhibitors specific to Erk1/2 and NF-κB eradicated the effect of PTH treatment on BMP2, BMP4, ALP and RUNX2 expression. These results demonstrate that PTH promotes the osteoblastic differentiation of endothelial cells via the Erk1/2 and NF-κB signaling pathways, which suggests a potential role of PTH in the promotion of VC. These findings provide an insight into the association between PTH and cardiovascular disease.

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Association of increased parathyroid hormone with neuroendocrine activation and endothelial dysfunction in elderly men with heart failure

Cited by 34 publications

References 44 publications

Functional proteomic analysis reveals sex-dependent differences in structural and energy-producing myocardial proteins in rat model of alcoholic cardiomyopathy

Functional proteomic analysis reveals sex-dependent differences in structural and energy-producing myocardial proteins in rat model of alcoholic cardiomyopathy

Cardiovascular diseases in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links

Parathyroid hormone promotes osteoblastic differentiation of endothelial cells via the extracellular signal‑regulated protein kinase 1/2 and nuclear factor‑κB signaling pathways

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