C-type natriuretic peptide immunoreactivity in human breast vascular endothelial cells

Heublein, Denise M.; Clavell, Alfredo L.; Stingo, A. J.; Lerman, Amir; Wold, Lester E.; Burnett, John C.

doi:10.1016/0196-9781(92)90065-b

Cited by 46 publications

(17 citation statements)

References 11 publications

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“…CNP is expressed in the vascular endothelium (Heublein et al 1992;Kohno et al 1992;Porter et al 1992;Stingo et al 1992a,b;Suga et al 1992) and is a potent growth inhibitor of SMCs. In addition, the production of CNP by aortic bovine endothelial cells in culture is potently stimulated by TGF-␤ (Suga et al 1992), which is highly expressed at the site of vascular injury.…”

Section: Discussionmentioning

confidence: 99%

Natriuretic Peptide System Gene Expression in Human Coronary Arteries

Casco

Veinot

Bold

et al. 2002

J Histochem Cytochem.

111

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S U M M A R YThe natriuretic peptides (NPs) ANF, BNP, and CNP have potent anti-proliferative and anti-migratory effects on vascular smooth muscle cells (SMCs). These properties make NPs relevant to the study of human coronary atherosclerosis because vascular cell proliferation and migration are central to the pathophysiology of atherosclerosis. However, the existence and cytological distribution of NPs and their receptors in human coronary arteries remain undetermined. This has hampered the development of hypotheses regarding the possible role of NPs in human coronary disease. We determined the pattern of expression of NPs and their receptors (NPRs) in human coronary arteries with atherosclerotic lesions classified by standard histopathological criteria as fatty streak/early atherosclerotic lesions, intermediate plaques, or advanced lesions. The investigation was carried out using a combination of immunocytochemistry (ICC), in situ hybridization (ISH), and semiquantitative polymerase chain reaction (PCR). Both by ICC and ISH, ANF was found in the intimal and medial layers of all lesions. BNP was highly expressed in advanced lesions where it was particularly evident by a strong ISH signal but weak ICC staining. CNP was demonstrable in all types of lesions, giving a strong signal by ISH and ICC. This peptide was particularly demonstrable in the endothelium, as well as in the SMCs of the intima, media, and vasa vasorum of the adventitia and in macrophages. By ISH, NPR-A was not detectable in any of the lesions but both NPR-B and NPR-C were found in the intimal and the inner medial layers. By RT-PCR, mRNA levels of all NPs tended to be increased in macroscopically diseased arteries, but only the values for BNP were significantly so. No significant changes in NPR mRNA levels were detected by PCR. In general, the signal intensity given by the NPs and their receptors by ICC or ISH appeared dependent on the type of lesion, being strongest in intermediate plaques and decreasing with increasing severity of the lesion. This study constitutes the first demonstration of NPs and NPR mRNAs in human coronary arteries and supports the existence of an autocrine/paracrine NP system that is actively modulated during the progression of atherosclerotic coronary disease. This suggests that the coronary NP system is involved in the pathobiology of intimal plaque formation in humans and may be involved in vascular remodeling.

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Section: Discussionmentioning

confidence: 99%

Natriuretic Peptide System Gene Expression in Human Coronary Arteries

Casco

Veinot

Bold

et al. 2002

J Histochem Cytochem.

111

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“…Further, ANP is ofcardiac origin and functions as a circulating hormone. In contrast, CNP is synthesized and released from endothelial cells (12)(13)(14), consistent with a paracrine role in the control of vascular tone ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

Vasonatrin peptide: a unique synthetic natriuretic and vasorelaxing peptide.

Wei¹,

Kim²,

Miller³

et al. 1993

J. Clin. Invest.

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This study reports the cardiovascular and renal actions of a novel and newly synthesized 27-amino acid peptide termed vasonatrin peptide (VNP). VNP is a chimera of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP). This synthetic peptide possesses the 22-amino acid structure of CNP, which is a cardiovascular selective peptide of endothelial origin and is structurally related to ANP. VNP also possesses the five-amino acid COOH terminus of ANP. The current study demonstrates both in vitro and in vivo that VNP possesses the venodilating actions of CNP, the natriuretic actions of ANP, and unique arterial vasodilating actions not associated with either ANP or CNP. (J. Clin. Invest. 1993. 92:2048-2052

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“…CNP consists of 22 amino acid residues and shares a 17-amino acid disulfide ring structure with atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) (29). CNP functions as a paracrine hormone in both the pulmonary and systemic circulations and is expressed and secreted by vascular endothelial cells (17,35,37). Like ANP and BNP, CNP has been demonstrated to relax blood vessels in a number of vascular beds (8,14,20,39,40).…”

mentioning

confidence: 99%

Mechanism of C-type natriuretic peptide-induced endothelial cell hyperpolarization

Simon¹,

Harrington²,

Liu³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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natriuretic peptide (CNP) has a demonstrated hyperpolarizing effect on vascular smooth muscle cells. However, its autocrine function, including its electrophysiological effect on endothelial cells, is not known. Here, we report the effect of CNP on the membrane potential (E m) of pulmonary microvascular endothelial cells and describe its target receptors, second messengers, and ion channels. We measured changes in E m using fluorescence imaging and perforated patch-clamping techniques. In imaging experiments, samples were preincubated in the potentiometric dye DiBAC4(3), and subsequently exposed to CNP in the presence of selective inhibitors of ion channels or second messengers. CNP exposure induced a dose-dependent decrease in fluorescence, indicating that CNP induces endothelial cell hyperpolarization. CNP-induced hyperpolarization was inhibited by the K ϩ channel blockers, tetraethylammonium or iberiotoxin, the nonspecific cation channel blocker, La 3ϩ , or by depletion or repletion of extracellular Ca 2ϩ or K ϩ , respectively. CNP-induced hyperpolarization was also blocked by pharmacological inhibition of PKG or by small interfering RNA (siRNA)-mediated knockdown of natriuretic peptide receptor-B (NPR-B). CNP-induced hyperpolarization was mimicked by the PKG agonist, 8-bromo-cGMP, and attenuated by both the endothelial nitric oxide synthase (eNOS) inhibitor, N -nitro-L-arginine methyl ester (L-NAME), and the soluble guanylyl cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. Presence of iberiotoxinsensitive, CNP-induced outward current was confirmed by perforated patch-clamping experiments. We conclude that CNP hyperpolarizes pulmonary microvascular endothelial cells by activating large-conductance calcium-activated potassium channels mediated by the activation of NPR-B, PKG, eNOS, and sGC.large-conductance calcium-activated potassium channels; ion channel C-TYPE NATRIURETIC PEPTIDE (CNP) is a highly conserved member of the natriuretic peptide family and an important, but controversial, regulator of vascular tone and blood pressure. CNP consists of 22 amino acid residues and shares a 17-amino acid disulfide ring structure with atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) (29). CNP functions as a paracrine hormone in both the pulmonary and systemic circulations and is expressed and secreted by vascular endothelial cells (17,35,37). Like ANP and BNP, CNP has been demonstrated to relax blood vessels in a number of vascular beds (8,14,20,39,40). Furthermore, CNP appears to have both anti-inflammatory (18, 26, 33) and anti-mitogenic (12, 18, 26) properties. Thus CNP may serve a potentially useful therapeutic agent, especially in the pulmonary circulation, where it has been found to attenuate both bleomycin-induced lung fibrosis and monocrotaline-induced pulmonary hypertension (18, 26). However, although the physiological effects of CNP are intriguing, the signaling mechanisms that underlie many of its vascular activities remain incompletely described.The physiological ...

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C-type natriuretic peptide immunoreactivity in human breast vascular endothelial cells

Cited by 46 publications

References 11 publications

Natriuretic Peptide System Gene Expression in Human Coronary Arteries

Natriuretic Peptide System Gene Expression in Human Coronary Arteries

Vasonatrin peptide: a unique synthetic natriuretic and vasorelaxing peptide.

Mechanism of C-type natriuretic peptide-induced endothelial cell hyperpolarization

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