Parathyroid hormone-related protein in the cardiovascular system.

Abstract

PTH-related protein (PTHrP) is expressed in a stretch-responsive manner in several types of smooth muscle. We previously demonstrated the production of PTHrP in adult rat heart muscle. In this study, we demonstrate the production of PTHrP in the cardiovascular systems of several mammalian species, including human. We demonstrate PTHrP by immunohistology, using a panel of murine monoclonal antibodies to PTHrP epitopes that span the entire length of the human PTHrP amino acid sequence, quantitate the concentration of PTHrP in the rat cardiovascular system by region-specific RIAs, and measure the relative levels of PTHrP messenger RNA (mRNA) by competitive polymerase chain reaction. Immunohistology studies demonstrated the presence of PTHrP in the cardiovascular systems of humans, rats, pigs, and rabbits. The most robust expression was found in atria, followed by the large vessels, then ventricles. No difference was seen between the left and right sides of the heart. Double staining procedures revealed that PTHrP and atrial naturietic peptide were coexpressed in some cells. Using RIAs and polymerase chain reaction, we demonstrated that atria contained a higher concentration of PTHrP than ventricles and that the relative PTHrP concentrations correlated to its mRNA concentrations in these two tissues. The concentrations of PTHrP in the smooth muscle surrounding the aorta and vena cava were comparable to those in atria. However, in these large vessels, the higher PTHrP levels did not correspond to its mRNA levels. Whereas the immunoreactive concentrations of PTHrP were similar in the atria, aorta, and vena cava, the mRNA levels in the aorta and vena cava were 3-fold lower than those in the atria. Certain PTHrP epitopes appeared to be differentially expressed in specific cardiovascular tissues. A comparison of region-specific assays showed that immunoreactivity measured by immunoassays to PTHrP-(38-64) and PTHrP-(109-141) were 3- to 5-fold greater than that determined by an immunoassay to PTHrP-(1-34). Our observations demonstrate that the atria, aorta, and vena cava contain the greatest amounts of PTHrP in the cardiovascular system. The discrepancy between the concentrations of PTHrP and its mRNA present in the aorta and vena cava suggest that the two may be regulated differently in these tissues. The widespread distribution of PTHrP suggests an important function for the protein in the cardiovascular system, possibly functioning as the calcium counterpart for the atrial natriuretic-sodium regulatory axis.