Correlation between plasma concentrations of calcitonin gene related peptide and pulmonary pressure in patients with systemic sclerosis

Bartosik, I; Eskilsson, Jan; Ekman, Rolf; Åkesson, Anita; Scheja, Agneta

doi:10.1136/ard.61.3.261

Cited by 14 publications

(8 citation statements)

References 13 publications

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“…22) Recently, it was found that in patients with systemic sclerosis and pulmonary hypertension, there is a positive correlation between CGRP and systolic pulmonary arterial pressure. 23) The similar positive correlation between CGRP and pulmonary pressure in our study suggests that changes in pulmonary arterial pressure may possibly play a role in the mechanism of CGRP production. Tjen, et al previously showed that exogenous CGRP reduced pulmonary artery pressure in hypobaric hypoxic rats.…”

Section: Discussionsupporting

confidence: 66%

Increased Circulating Calcitonin Gene-Related Peptide in Congestive Heart Failure Caused by Congenital Heart Disease

et al. 2005

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SUMMARYCalcitonin gene-related peptide has potent vasodilatory and inotropic actions. The aim of this study was to characterize the changes in this peptide in children with varying degrees of heart failure secondary to congenital heart disease with left to right shunt and to assess its relationship to systolic pulmonary arterial pressure.Plasma calcitonin gene-related peptide levels were measured in 131 children including 13 healthy ones, 43 with various degrees of heart failure secondary to congenital heart disease, and 75 with congenital heart disease without heart failure.In patients with heart failure, calcitonin gene-related peptide concentrations were markedly elevated (15.8 ± 2.1 pg/mL) as compared with healthy control subjects (7.0 ± 0.8 pg/mL, P < 0.05) or patients with congenital heart disease but without heart failure (18.6 ± 1.2 pg/mL, P < 0.01). Compared with the controls, there were highly significant stepwise increases in the calcitonin gene-related peptide levels in the mild (n = 15), moderate (n = 12), and severe (n = 16) heart failure subgroups by 1.5, 1.7 and 3.4 fold, respectively. The plasma calcitonin gene-related peptide levels also correlated directly with the pulmonary arterial systolic pressure (r = 0.515, P < 0.0001).The results of this study indicate that congestive heart failure secondary to congenital heart disease with increased pulmonary flow is associated with elevated levels of calcitonin gene-related peptide that are related to disease severity. Pulmonary overcirculation may play a role in upregulation of calcitonin gene-related peptide in congestive heart failure. (Int Heart J 2005; 46: 867-875)

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Section: Discussionsupporting

confidence: 66%

Increased Circulating Calcitonin Gene-Related Peptide in Congestive Heart Failure Caused by Congenital Heart Disease

et al. 2005

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“…Interestingly, patients with higher CGRP levels had more severe PAH ( Bartosik et al, 2002 ; Zhang et al, 2006 ). Likewise, chronic hypoxia-induced PH in rats was associated with higher levels of CGRP.…”

Section: Investigation Of C-fiber-derived Neuropeptides As Novel Pulmmentioning

confidence: 99%

The Regulation of Pulmonary Vascular Tone by Neuropeptides and the Implications for Pulmonary Hypertension

Moosavi

Bubb

2018

Front. Physiol.

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Pulmonary hypertension (PH) is an incurable, chronic disease of small pulmonary vessels. Progressive remodeling of the pulmonary vasculature results in increased pulmonary vascular resistance (PVR). This causes secondary right heart failure. PVR is tightly regulated by a range of pulmonary vasodilators and constrictors. Endothelium-derived substances form the basis of most current PH treatments. This is particularly the case for pulmonary arterial hypertension. The major limitation of current treatments is their inability to reverse morphological changes. Thus, there is an unmet need for novel therapies to reduce the morbidity and mortality in PH. Microvessels in the lungs are highly innervated by sensory C fibers. Substance P and calcitonin gene-related peptide (CGRP) are released from C-fiber nerve endings. These neuropeptides can directly regulate vascular tone. Substance P tends to act as a vasoconstrictor in the pulmonary circulation and it increases in the lungs during experimental PH. The receptor for substance P, neurokinin 1 (NK1R), mediates increased pulmonary pressure. Deactivation of NK1R with antagonists, or depletion of substance P prevents PH development. CGRP is a potent pulmonary vasodilator. CGRP receptor antagonists cause elevated pulmonary pressure. Thus, the balance of these peptides is crucial within the pulmonary circulation (Graphical Abstract). Limited progress has been made in understanding their impact on pulmonary pathophysiology. This is an intriguing area of investigation to pursue. It may lead to promising new candidate therapies to combat this fatal disease. This review provides a summary of the current knowledge in this area. It also explores possible future directions for neuropeptides in PH.

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“…The distribution of IMD/AM2 specifically in human pulmonary vasculature is relatively unknown. CGRP [21] and AM [22] are both elevated in plasma of PAH patients. CLR is expressed by the pulmonary microvascular endothelium [23] and within alveolar capillaries [24] and bronchial venules [25].…”

Section: Introductionmentioning

confidence: 94%

Protective effects of intermedin/adrenomedullin-2 in a cellular model of human pulmonary arterial hypertension

et al. 2020

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Proliferation of pulmonary fibroblasts (PF) and distal migration of smooth muscle cells (PSM) are hallmarks of pulmonary arterial hypertension (PAH). Intermedin/adrenomedullin-2 (IMD/AM2) belongs to the Calcitonin Gene-Related Peptide (CGRP)/Adrenomedullin (AM) superfamily. These peptides act via Calcitonin-Like Receptors (CLR) combined with one of three Receptor activity-modifying proteins (RAMPs). IMD/AM2 is a potent pulmonary vasodilator in animal studies. The aim was to describe expression of IMD/AM2, AM and receptor components in human pulmonary vascular cells and to elucidate effects of IMD/AM2 on human PSM migration and PF proliferation. Gene expression was detected by immunofluorescence, immunoblotting and qRT-PCR. Normotension and hypertension were simulated by applying pulsatile mechanical stretch (Flexcell® apparatus). Viable cell numbers were determined by dye exclusion. PSM chemotaxis was measured via Dunn chamber. IMD/AM2 protein was co-expressed with AM and their receptor components in pulmonary artery and microvascular endothelial (PAEC, PMVEC) and non-endothelial cells (PF, PSM), and localised to vesicles. IMD/AM2 was secreted under basal conditions, most abundantly from PF and PMVEC. Secretion from PF and PSM was enhanced by stretch. IMD/AM2 mRNA expression increased in response to hypertensive stretch of PSM. IMD/AM2 inhibited PDGF (10 −7 M)-mediated PSM migration maximally at 3 × 10-10 M and PF proliferation maximally at 3 × 10-9 M. Angiotensin II (5 × 10-8 M), normotensive and hypertensive stretch augmented PF proliferation. IMD/AM2 (10-9 M) abolished the proliferative effects of Angiotensin II and normotensive stretch and attenuated the proliferative effect of hypertensive stretch alone and combined with angiotensin II. These findings indicate an important counter-regulatory role for IMD/AM2 in PAH.

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Correlation between plasma concentrations of calcitonin gene related peptide and pulmonary pressure in patients with systemic sclerosis

Cited by 14 publications

References 13 publications

Increased Circulating Calcitonin Gene-Related Peptide in Congestive Heart Failure Caused by Congenital Heart Disease

Increased Circulating Calcitonin Gene-Related Peptide in Congestive Heart Failure Caused by Congenital Heart Disease

The Regulation of Pulmonary Vascular Tone by Neuropeptides and the Implications for Pulmonary Hypertension

Protective effects of intermedin/adrenomedullin-2 in a cellular model of human pulmonary arterial hypertension

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