Progenitor Cells In Hypertension Research Articles

Identification of Free Nitric Oxide Radicals in Rat Bone Marrow: Implications for Progenitor Cell Mobilization in Hypertension

Nitric oxide (NO) has been implicated in matrix metallopeptidase 9 (MMP9)-dependent mobilization of hematopoietic stem and progenitor cells from bone marrow (BM). However, direct measurement of NO in the BM remained elusive due to its low in situ concentration and short lifetime. Using NO spin trapping and electron paramagnetic resonance (EPR) spectroscopy we give the first experimental confirmation of free NO radicals in rodent BM. NO production was quantified and attributed to enzymatic activity of NO synthases (NOS). Although endothelial NOS (eNOS) accounts for most (66%) of basal NO, we identified a significant contribution (23%) from inducible NOS (iNOS). Basal NO levels closely correlate with MMP9 bioavailability in BM of both hypertensive and control rats. Our observations support the hypothesis that inadequate mobilization of BM-derived stem and progenitor cells in hypertension results from impaired NOS/NO/MMP9 signalling in BM, a condition that may be corrected with pharmacological intervention.

Accelerated senescence of endothelial progenitor cells in hypertension is related to the reduction of calcitonin gene-related peptide

To explore whether the accelerated senescence of endothelial progenitor cells (EPCs) is related to the reduction of calcitonin gene-related peptide (CGRP) in hypertension. In-vivo studies, plasma levels of CGRP and the number of senescent EPCs were measured in hypertensive humans and animals, from which the EPCs were isolated to examine the production of CGRP. Moreover, rutaecarpine, as an agent or tool to stimulate CGRP production, was used in hypertensive animals. The effects of rutaecarpine on angiotensin II-induced EPCs senescence were evaluated in vitro. The results showed that the number of circulating senescent EPCs was significantly increased in hypertension concomitantly with the decreased plasma level of CGRP and the decreased CGRP mRNA expression in EPCs. Administration of rutaecarpine reversed EPC senescence along with an elevation in CGRP production in spontaneously hypertensive rats. In the angiotensin II-induced EPCs senescence, the CGRP mRNA expression was reduced, which was reversed by rutaecarpine. The effect of rutaecarpine on EPCs was canceled in the presence of capsazepine, a selective antagonist of transient receptor potential vanilloid 1. The results suggest that CGRP may work as an endogenous protective substance to counteract EPCs senescence in hypertension and the accelerated EPCs senescence in hypertension was related to the reduction of CGRP.

腎疾患の進展阻止を目指した新しい治療戦略の開発

We provide a research update regarding novel therapeutic strategies to prevent the development of kidney disease and summarize the latest proceedings in this field. Chronic progressive kidney disease carries severe consequences and has limited treatment options. The purpose of this review is two-fold. The first aim is to provide a concise overview of the strategies of gene therapy, including pyrrole-imidazole polyamides (PI polyamides). PI polyamides are a new type of small compound that inhibit gene expression by binding to the minor groove of DNA. A PI polyamide that targets rat transforming growth factor-β1 was designed as a gene-silencing agent for progressive kidney disease. In the future, control of gene expression by PI polyamides may ameliorate progressive kidney diseases that are not treatable with current medicine. Future therapeutic strategies aimed at alteration of the immune responses through manipulation of Fcγ receptor interactions by the use of PI polyamides could be explored in the model of lupus nephritis. Thus Fcγ receptor gene therapy provides an attractive strategy to develop an immunotherapy as a general treatment option. The second aim is to summarize the published data regarding the role of bone marrow stem cells in renal repair after acute and chronic kidney injury. Currently, much of our knowledge of renal protective effect of dedifferentiated fat (DFAT) cells is obtained through animal research. The results to date indicate that DFAT cells may provide a source for cell therapy for severe progressive kidney disease. Our goal is to understand the mechanism of renal protection by DFAT cells and to develop stratagems utilizing DFAT cells for the eventual treatment of patients with kidney disease. The importance of conservative regenerative medicine has recently been demonstrated. It has become apparent that angiotensin II receptor blockade (ARB) improves the proliferation and function of endothelial progenitor cells in hypertension, suggesting that ARB is useful to repair hypertensive renal injury. In this review, we will focus on the role of gene therapy and regenerative medicine as therapeutic modalities in kidney disease.