Relaxin, a Potent Microcirculatory Effector, Is Not Angiogenic

Norrby, Klas; Bani, Danièle; Bigazzi, Mario; Sacchi, T. Banni

doi:10.1159/000179178

Cited by 10 publications

(5 citation statements)

References 23 publications

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“…In vivo, many pharmacological studies, as well as toxicology safety studies, using systemic administration of relaxin have shown the absence of any angiopathies or hypotension associated with systemic administration of cytokines known to have direct effects on endothelial cells, such as VEGF or bFGF. Previous reports have shown directly that relaxin infusion into a normal omental vascular bed will not cause proliferation of vessels 16 . This finding is consistent with the hypothesis that endothelial cells do not proliferate when exposed to relaxin.…”

Section: Resultssupporting

confidence: 90%

Relaxin induces vascular endothelial growth factor expression and angiogenesis selectively at wound sites

Unemori¹,

Lewis²,

Constant

et al. 2000

Wound Repair Regeneration

139

121

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Relaxin is a reproductive hormone that has historically been characterized as being responsible for pubic ligament loosening and cervical ripening. Recently, relaxin has been associated with neovascularization of the endometrial lining of the uterus, potentially via specific induction of vascular endothelial growth factor. Previously conducted clinical studies using partially purified porcine relaxin have described relaxin's ability to stimulate the healing of ischemic wounds, suggesting that relaxin may also have angiogenic effects at sites of ischemic wound healing. In the present study, relaxin's angiogenic effects in the context of wound repair were tested in rodent models of angiogenesis and wound healing. Relaxin showed an ability to stimulate new blood vessel formation, particularly at ischemic wound sites, and to induce both vascular endothelial growth factor and basic fibroblast growth factor specifically in cells, presumably including macrophages, collected from wound sites. Resident macrophages collected from nonwound sites, such as the lung, did not show altered expression of these cytokines following relaxin administration. Because angiogenic wound cells are frequently macrophages, THP-1 cells, a cell line of monocyte lineage that binds relaxin specifically, were tested for and shown to induce vascular endothelial growth factor and basic fibroblast growth factor in response to relaxin. In conclusion, relaxin may be useful in the treatment of ischemic wounds by stimulating angiogenesis via the induction of vascular endothelial growth factor and basic fibroblast growth factor in wound macrophages.

show abstract

Section: Resultssupporting

confidence: 90%

Relaxin induces vascular endothelial growth factor expression and angiogenesis selectively at wound sites

Unemori¹,

Lewis²,

Constant

et al. 2000

Wound Repair Regeneration

139

121

View full text Add to dashboard Cite

show abstract

“…Interestingly, VEGF mRNA expression was not enhanced by rhRLX in resident macrophages in the lung or spleen remote from the site of injury. Nor did rhRLX have any direct angiogenic effects on cultured endothelial cells, confirming an earlier report (73). Finally, rhRLX increased VEGF 165 and 120, as well as bFGF mRNA expression by THP-1 cells, a human monocyte/macrophage cell line.…”

Section: Rlx and Angiogenesissupporting

confidence: 87%

Emerging role of relaxin in renal and cardiovascular function

Conrad

Novak

2004

American Journal of Physiology-Regulatory, Integrative and Comp

136

113

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Conrad, Kirk P., and Jacqueline Novak. Emerging role of relaxin in renal and cardiovascular function. Am J Physiol Regul Integr Comp Physiol 287: R250 -R261, 2004; 10.1152/ajpregu.00672.2003.-Although traditionally associated with reproductive processes, relaxin is emerging as an important player in renal and cardiovascular function. Much of our recently acquired understanding of relaxin in this new context has arisen from studies of maternal renal and cardiovascular adaptations to pregnancy in rats where the hormone is turning out to be an important mediator. First, we highlight the influence of relaxin on renal hemodynamics and glomerular filtration rate, as well as on other peripheral circulations. Second, we discuss the effect of relaxin on both the steady and pulsatile systemic arterial load, as well as on the heart, in particular, coronary blood flow. Third, we consider the impact of the hormone on cultured endothelial and vascular smooth muscle cells. Fourth, we address the interaction of relaxin with renal and cardiac disease, as well as its role in angiogenesis. Finally, in Perspectives, we point out several key research questions in need of investigation that relate to a potential autocrine/paracrine role of relaxin in renal and cardiovascular tissues. Furthermore, on the basis of its potent vasodilatory and matrix-degrading attributes, we speculate about the therapeutic potential of relaxin in renal and cardiovascular diseases. pregnancy; kidney circulation; glomerular filtration; osmoregulation; peripheral circulation; systemic hemodynamics; vasodilation; arterial compliance; heart; myogenic reactivity; angiogenesis; relaxin receptors; matrix metalloproteinase; gelatinase; endothelin B receptor; nitric oxide; angiotensin II THE OBJECTIVE OF THIS REVIEW is to highlight the new and emerging roles of relaxin (RLX) in the renal and cardiovascular systems. Traditionally, RLX has been tied to reproductive processes during pregnancy, because most investigations conducted by reproductive biologists have dealt with the hormone in this context. The traditional sources of RLX have been reproductive tissues such as the corpus luteum of the ovary from which the hormone emanates and circulates during the luteal phase of the menstrual cycle and during pregnancy in women (95). Furthermore, there has been no well-established role in the male. However, the concept of a role for RLX in cardiovascular function actually has its antecedents early on in the history of RLX research, when Frederick L. Hisaw, who discovered the hormone (47, 113), noted that after administration of RLX to castrated monkeys, there were marked morphological changes in the endothelial cells of the endometrium consistent with hypertrophy and hyperplasia (48). The concept that RLX can affect blood vessel structure and function has since gained considerable support, particularly in the last decade. Much of our recently gained knowledge of RLX in this new light has arisen from studies of maternal renal and cardiovascular function in the gravid rat mo...

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“…Computer-assisted morphometry of sinusoids was performed on the semithin sections as described previously for similar purposes (Norrby et al 1996). Two different liver fragments per rat were used.…”

Section: Liver Sinusoids and Relaxin · D Bani And Others 543mentioning

confidence: 99%

The vasorelaxant hormone relaxin induces changes in liver sinusoid microcirculation: a morphologic study in the rat

Bani

Nistri²,

Quattrone³

et al. 2001

Journal of Endocrinology

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This study shows that specialized contractile endothelial cells exist in rat liver sinusoids which may be involved in the local control of hemodynamics and which are sensitive to vasoactive agents, including the vasorelaxant hormone relaxin. Male rats were treated with 10 µg relaxin for 4 days; phosphate-buffered saline (PBS)-treated rats were the controls. For comparison, rats treated with relaxin together with the NO-synthase inhibitor N -nitro--arginine methyl ester (L-NAME), and rats treated with the vasodilator taurodeoxycholic acid or the vasoconstrictor ethanol were investigated. Liver fragments were studied morphologically and morphometrically. In the control rats, peculiar contractile cells were present in the endothelial lining. These cells had abundant myofilaments and formed cytoplasmic blebs projecting into and often occluding the lumen. In the ethanol-treated rats, sinusoids were constricted and filled with cytoplasmic blebs. In the relaxintreated rats, sinusoids were markedly dilated and the cytoplasmic blebs nearly disappeared. Similar findings were observed in the taurodeoxycholic acid-treated rats. The effects of relaxin were blunted by L-NAME, suggesting that the relaxin action involves an NO-mediated mechanism.

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Relaxin, a Potent Microcirculatory Effector, Is Not Angiogenic

Cited by 10 publications

References 23 publications

Relaxin induces vascular endothelial growth factor expression and angiogenesis selectively at wound sites

Relaxin induces vascular endothelial growth factor expression and angiogenesis selectively at wound sites

Emerging role of relaxin in renal and cardiovascular function

The vasorelaxant hormone relaxin induces changes in liver sinusoid microcirculation: a morphologic study in the rat

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