Biopterin status in dogs with myxomatous mitral valve disease is associated with disease severity and cardiovascular risk factors

Maria Josefine Reimann; J. Häggström; Alan Mortensen; Jens Lykkesfeldt; Jacob Eifer Møller; Bo Torkel Falk; Lisbeth Høier Olsen

doi:10.1111/jvim.12425

Biopterin status in dogs with myxomatous mitral valve disease is associated with disease severity and cardiovascular risk factors

Maria Josefine Reimann, J. Häggström, Alan Mortensen, Jens Lykkesfeldt, Jacob Eifer Møller, Bo Torkel Falk, Lisbeth Høier Olsen

Lifepharm

12 Citations (Scopus)

Abstract

Background: Endothelial dysfunction (ED) has been suggested to be associated with myxomatous mitral valve disease (MMVD) in dogs. Tetrahydrobiopterin (BH4) is an important cofactor for production of the endothelium-derived vasodilator nitric oxide (NO). Under conditions of oxidative stress, BH4 is oxidized to the biologically inactive form dihydrobiopterin (BH2). Thus, plasma concentrations of BH2 and BH4 may reflect ED and oxidative stress. Objective: To determine plasma concentrations of BH2 and BH4 in dogs with different degrees of MMVD. Animals: Eighty-four privately owned dogs grouped according to ACVIM guidelines (37 healthy control dogs including 13 Beagles and 24 Cavalier King Charles Spaniels [CKCSs], 33 CKCSs with MMVD of differing severity including 18 CKCSs [group B1] and 15 CKCSs [group B2], and 14 dogs of different breeds with clinical signs of congestive heart failure [CHF] because of MMVD [group C]). Methods: Dogs underwent clinical examination including echocardiography. Plasma concentrations of BH2 and BH4 were measured using high-performance liquid chromatography with fluorescence detection. Results: Higher plasma BH4 and BH2 concentrations were found with dogs in CHF compared with all other groups (control, B1 and B2; P ≤ .001). Females had higher concentrations of BH4 and BH4/BH2 (P ≤ .0003). BH4/BH2 was found to decrease with age (P < .0001). Cardiovascular risk factors in humans such as passive smoking (P ≤ .01) and increased body weight (P ≤ .009) were associated with lower BH4 concentrations. Conclusions and Clinical Importance: Age, sex, body weight, passive smoking, and cardiac status are associated with plasma biopterin concentration in dogs. Additional studies should clarify the clinical implications of the findings.

Original language	English
Journal	Journal of veterinary internal medicine / American College of Veterinary Internal Medicine
Volume	28
Issue number	5
Pages (from-to)	1520-1526
Number of pages	7
ISSN	0891-6640
DOIs	https://doi.org/10.1111/jvim.12425
Publication status	Published - 1 Sept 2014

Keywords

Faculty of Health and Medical Sciences
Endothelial dysfunction
Mitral regurgitation
Oxidative stress
Tetrahydrobiopterin

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10.1111/jvim.12425

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Reimann, M. J., Häggström, J., Mortensen, A., Lykkesfeldt, J., Møller, J. E., Falk, B. T., & Olsen, L. H. (2014). Biopterin status in dogs with myxomatous mitral valve disease is associated with disease severity and cardiovascular risk factors. Journal of veterinary internal medicine / American College of Veterinary Internal Medicine, 28(5), 1520-1526. https://doi.org/10.1111/jvim.12425

Biopterin status in dogs with myxomatous mitral valve disease is associated with disease severity and cardiovascular risk factors. / Reimann, Maria Josefine; Häggström, J.; Mortensen, Alan et al.

In: Journal of veterinary internal medicine / American College of Veterinary Internal Medicine, Vol. 28, No. 5, 01.09.2014, p. 1520-1526.

Research output: Contribution to journal › Journal article › Research › peer-review

Reimann, MJ, Häggström, J, Mortensen, A, Lykkesfeldt, J, Møller, JE, Falk, BT & Olsen, LH 2014, 'Biopterin status in dogs with myxomatous mitral valve disease is associated with disease severity and cardiovascular risk factors', Journal of veterinary internal medicine / American College of Veterinary Internal Medicine, vol. 28, no. 5, pp. 1520-1526. https://doi.org/10.1111/jvim.12425

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title = "Biopterin status in dogs with myxomatous mitral valve disease is associated with disease severity and cardiovascular risk factors",

abstract = "Background: Endothelial dysfunction (ED) has been suggested to be associated with myxomatous mitral valve disease (MMVD) in dogs. Tetrahydrobiopterin (BH4) is an important cofactor for production of the endothelium-derived vasodilator nitric oxide (NO). Under conditions of oxidative stress, BH4 is oxidized to the biologically inactive form dihydrobiopterin (BH2). Thus, plasma concentrations of BH2 and BH4 may reflect ED and oxidative stress. Objective: To determine plasma concentrations of BH2 and BH4 in dogs with different degrees of MMVD. Animals: Eighty-four privately owned dogs grouped according to ACVIM guidelines (37 healthy control dogs including 13 Beagles and 24 Cavalier King Charles Spaniels [CKCSs], 33 CKCSs with MMVD of differing severity including 18 CKCSs [group B1] and 15 CKCSs [group B2], and 14 dogs of different breeds with clinical signs of congestive heart failure [CHF] because of MMVD [group C]). Methods: Dogs underwent clinical examination including echocardiography. Plasma concentrations of BH2 and BH4 were measured using high-performance liquid chromatography with fluorescence detection. Results: Higher plasma BH4 and BH2 concentrations were found with dogs in CHF compared with all other groups (control, B1 and B2; P ≤ .001). Females had higher concentrations of BH4 and BH4/BH2 (P ≤ .0003). BH4/BH2 was found to decrease with age (P < .0001). Cardiovascular risk factors in humans such as passive smoking (P ≤ .01) and increased body weight (P ≤ .009) were associated with lower BH4 concentrations. Conclusions and Clinical Importance: Age, sex, body weight, passive smoking, and cardiac status are associated with plasma biopterin concentration in dogs. Additional studies should clarify the clinical implications of the findings.",

keywords = "Faculty of Health and Medical Sciences, Endothelial dysfunction, Mitral regurgitation, Oxidative stress, Tetrahydrobiopterin",

author = "Reimann, {Maria Josefine} and J. H{\"a}ggstr{\"o}m and Alan Mortensen and Jens Lykkesfeldt and M{\o}ller, {Jacob Eifer} and Falk, {Bo Torkel} and Olsen, {Lisbeth H{\o}ier}",

note = "Copyright {\textcopyright} 2014 by the American College of Veterinary Internal Medicine.",

year = "2014",

month = sep,

day = "1",

doi = "10.1111/jvim.12425",

language = "English",

volume = "28",

pages = "1520--1526",

journal = "Journal of Veterinary Internal Medicine",

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T1 - Biopterin status in dogs with myxomatous mitral valve disease is associated with disease severity and cardiovascular risk factors

AU - Reimann, Maria Josefine

AU - Häggström, J.

AU - Mortensen, Alan

AU - Lykkesfeldt, Jens

AU - Møller, Jacob Eifer

AU - Falk, Bo Torkel

AU - Olsen, Lisbeth Høier

PY - 2014/9/1

Y1 - 2014/9/1

N2 - Background: Endothelial dysfunction (ED) has been suggested to be associated with myxomatous mitral valve disease (MMVD) in dogs. Tetrahydrobiopterin (BH4) is an important cofactor for production of the endothelium-derived vasodilator nitric oxide (NO). Under conditions of oxidative stress, BH4 is oxidized to the biologically inactive form dihydrobiopterin (BH2). Thus, plasma concentrations of BH2 and BH4 may reflect ED and oxidative stress. Objective: To determine plasma concentrations of BH2 and BH4 in dogs with different degrees of MMVD. Animals: Eighty-four privately owned dogs grouped according to ACVIM guidelines (37 healthy control dogs including 13 Beagles and 24 Cavalier King Charles Spaniels [CKCSs], 33 CKCSs with MMVD of differing severity including 18 CKCSs [group B1] and 15 CKCSs [group B2], and 14 dogs of different breeds with clinical signs of congestive heart failure [CHF] because of MMVD [group C]). Methods: Dogs underwent clinical examination including echocardiography. Plasma concentrations of BH2 and BH4 were measured using high-performance liquid chromatography with fluorescence detection. Results: Higher plasma BH4 and BH2 concentrations were found with dogs in CHF compared with all other groups (control, B1 and B2; P ≤ .001). Females had higher concentrations of BH4 and BH4/BH2 (P ≤ .0003). BH4/BH2 was found to decrease with age (P < .0001). Cardiovascular risk factors in humans such as passive smoking (P ≤ .01) and increased body weight (P ≤ .009) were associated with lower BH4 concentrations. Conclusions and Clinical Importance: Age, sex, body weight, passive smoking, and cardiac status are associated with plasma biopterin concentration in dogs. Additional studies should clarify the clinical implications of the findings.

AB - Background: Endothelial dysfunction (ED) has been suggested to be associated with myxomatous mitral valve disease (MMVD) in dogs. Tetrahydrobiopterin (BH4) is an important cofactor for production of the endothelium-derived vasodilator nitric oxide (NO). Under conditions of oxidative stress, BH4 is oxidized to the biologically inactive form dihydrobiopterin (BH2). Thus, plasma concentrations of BH2 and BH4 may reflect ED and oxidative stress. Objective: To determine plasma concentrations of BH2 and BH4 in dogs with different degrees of MMVD. Animals: Eighty-four privately owned dogs grouped according to ACVIM guidelines (37 healthy control dogs including 13 Beagles and 24 Cavalier King Charles Spaniels [CKCSs], 33 CKCSs with MMVD of differing severity including 18 CKCSs [group B1] and 15 CKCSs [group B2], and 14 dogs of different breeds with clinical signs of congestive heart failure [CHF] because of MMVD [group C]). Methods: Dogs underwent clinical examination including echocardiography. Plasma concentrations of BH2 and BH4 were measured using high-performance liquid chromatography with fluorescence detection. Results: Higher plasma BH4 and BH2 concentrations were found with dogs in CHF compared with all other groups (control, B1 and B2; P ≤ .001). Females had higher concentrations of BH4 and BH4/BH2 (P ≤ .0003). BH4/BH2 was found to decrease with age (P < .0001). Cardiovascular risk factors in humans such as passive smoking (P ≤ .01) and increased body weight (P ≤ .009) were associated with lower BH4 concentrations. Conclusions and Clinical Importance: Age, sex, body weight, passive smoking, and cardiac status are associated with plasma biopterin concentration in dogs. Additional studies should clarify the clinical implications of the findings.

KW - Faculty of Health and Medical Sciences

KW - Endothelial dysfunction

KW - Mitral regurgitation

KW - Oxidative stress

KW - Tetrahydrobiopterin

U2 - 10.1111/jvim.12425

DO - 10.1111/jvim.12425

M3 - Journal article

C2 - 25274442

SN - 0891-6640

VL - 28

SP - 1520

EP - 1526

JO - Journal of Veterinary Internal Medicine

JF - Journal of Veterinary Internal Medicine

IS - 5

ER -

Biopterin status in dogs with myxomatous mitral valve disease is associated with disease severity and cardiovascular risk factors

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