Sex-specific differences in ventricular expression and function of parathyroid hormone-related peptide*1

Grohé, Christian; Eickels, Martin van; Wenzel, Sibylle; Meyer, Rainer; Degenhardt, Heike; Doevendans, Pieter A.; Heinemann, Marcus P.; Ross, Günter; Schlüter, Klaus‐Dieter

doi:10.1016/j.cardiores.2003.11.025

Cited by 31 publications

(30 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sex-specific PTHrP effects are recognized in other settings; thus, it is not surprising to find these differences in lung cancer. For example, PTHrP augments coronary blood flow to a greater extent in female rats than in male rats (36). In addition, PTHrP stimulates nipple development in fetal mice but only in females (37).…”

Section: Discussionmentioning

confidence: 99%

Sex-Specific Survival Advantage with Parathyroid Hormone–Related Protein in Non–Small Cell Lung Carcinoma Patients

Hastings¹,

Laux²,

Casillas³

et al. 2006

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Parathyroid hormone^related protein (PTHrP) is commonly expressed in non^small cell lung carcinomas (NSCLC). Expression of the protein could have implications for progression of the disease because it regulates cancer cell growth, apoptosis, and angiogenesis. However, its relationship with survival has not been evaluated in a large-scale investigation. Experimental Design: PTHrP expression was assessed in paraffin-embedded tumor samples from 407 patients with NSCLC by immunohistochemistry. A pathologist unaware of the clinical history classified specimens as PTHrP positive or PTHrP negative. The log-rank test was used to compare survivals of PTHrP-positive and PTHrP-negative groups, and Cox regression was used to adjust for additional covariates.Results: Median survival was 55 versus 22 months (P < 0.001) in female patients with and without tumor PTHrP, respectively. Male survival was 38 months independent of PTHrP status. Stage, histology, age, and smoking history were also associated with increased longevity. PTHrP remained a significant predictor of survival for female patients after controlling for stage, histology, and age. Conclusions: In this study, PTHrP expression was associated with a survival advantage in female patients. Additional investigations must be done to ascertain whether the result is reproducible and independent of potential confounding covariates. Sex-dependent effects of PTHrP in lung cancer would open new avenues of research into the role of sex in cancer progression.Parathyroid hormone-related protein (PTHrP) was discovered as the factor responsible for hypercalcemia of malignancy. As the name implies, PTHrP shares structural similarities with PTH, specifically in the NH 2 -terminal 34 amino acids. Consequently, PTHrP 1-34 binds to the same receptor as PTH 1-34, the type 1 PTH/PTHrP receptor (PTH1R), and duplicates the effects of PTH 1-34 in tissues that bear the receptor, including causing hypercalcemia. Hypercalcemic effects are mediated through decreases in calcium excretion in kidney and increases in calcium release from bone. It is less widely appreciated that PTHrP also exerts effects direct effects on cancer cells that could be important in the pathology of malignancy.

show abstract

Section: Discussionmentioning

confidence: 99%

Sex-Specific Survival Advantage with Parathyroid Hormone–Related Protein in Non–Small Cell Lung Carcinoma Patients

Hastings¹,

Laux²,

Casillas³

et al. 2006

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Experiments were performed on isolated hearts from male Wistar rats (4 months old; weighing 225-275 g) as previously described (Grohé et al 2004). Hearts were rapidly excised and the aorta was cannulated for retrograde perfusion with a 16-gauge needle connected to a Langendorff perfusion system.…”

Section: Langendorff Perfusionmentioning

confidence: 99%

Rat intermedin1-47 does not improve functional recovery in postischemic hearts

Münzel

Schlier

Schreckenberg

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

Intermedin, a novel member of the calcitonin/calcitonin gene-related peptide family identified from vertebrate genomes, may directly affect cardiac function but current studies revealed no clear picture. The aims of our study were to compare direct contractile effects of intermedin on cardiomyocytes to that on the whole organ and to investigate whether intermedin improves postischemic recovery independent of an effect on acute reperfusion injury. Isolated adult rat ventricular cardiomyocytes were electrically paced and cell shortening was monitored as a readout associated to cardiac performance. Calcium transients were analyzed by Fura-2AM loading of these cells. Isolated rat hearts were investigated by Langendorff perfusion under nonischemic conditions and after 45-min no-flow ischemia followed up by 30-min reperfusion prior to drug testing. Intermedin caused a positive contractile effect on cardiomyocytes that was mediated by protein kinase A activation and accompanied by improved calcium transients. In contrast, intermedin reduced left ventricular developed pressure in Langendorff-perfused rat hearts. This negative inotropic effect was attenuated by inhibition of nitric oxide synthesis. In postischemic hearts (impaired nitric oxide synthesis), the negative inotropic effect was attenuated but no positive inotropic effect occurred. However, intermedin caused robust vasodilation in nonischemic and postischemic hearts. Our findings suggest that the peptide binds preferentially to vascular cells in the intact organ. The loss of nitric oxide induction in postischemic hearts attenuates a negative inotropic effect of intermedin but does not improve cardiac performance independent of acute reperfusion injury.

show abstract

“…In recent studies, Monego et al (27) have found that PTHrP was released in human ventricular cardiomyocytes on ischemic injury (27), and PTHrP has been reported to improve postischemic cardiac contractile function (18,25). Interestingly, PTHrP expression has been found to be modulated by estrogen, and PTHrP improved postischemic cardiac function to a greater extent in females than in males after I/R injury (11). Therefore, besides activating the cardioprotective signaling kinases, activation of CaSR could also lead to release of PTHrP, which could have additional protective effects.…”

Section: Discussionmentioning

confidence: 99%

Calcium-sensing receptor: a sensor and mediator of ischemic preconditioning in the heart

Sun

Murphy

2010

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

Sex-specific differences in ventricular expression and function of parathyroid hormone-related peptide*1

Abstract: Sex determines the ventricular expression of PTHrP mRNA and protein. The results indicate that PTHrP may improve cardiac function to a greater extent in women than in men following a brief period of ischemia.

Cited by 31 publications

References 20 publications

Sex-Specific Survival Advantage with Parathyroid Hormone–Related Protein in Non–Small Cell Lung Carcinoma Patients

Sex-Specific Survival Advantage with Parathyroid Hormone–Related Protein in Non–Small Cell Lung Carcinoma Patients

Rat intermedin1-47 does not improve functional recovery in postischemic hearts

Calcium-sensing receptor: a sensor and mediator of ischemic preconditioning in the heart

Contact Info

Product

Resources

About