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Therapeutic potential of folic acid supplementation for cardiovascular disease prevention through homocysteine lowering and blockade in rheumatoid arthritis patients.

Essouma M, Noubiap JJ - Biomark Res (2015)

Bottom Line: Rheumatoid arthritis (RA) is a chronic inflammatory disease that preferentially affects joints, and characterized by an approximately two-fold increased risk of cardiovascular diseases compared with the general population.Beyond classical cardiovascular risk factors, systemic inflammatory markers are primarily involved.Indeed, hyperhomocysteinemia is commonly found in RA patients as a result of both genetic and non-genetic factors including older age, male gender, disease-specific features and disease-modifying antirheumatic drugs.

View Article: PubMed Central - PubMed

Affiliation: Division of Medicine, Sangmelima Referral Hospital, P.O. Box 890, Sangmelima, Cameroon.

ABSTRACT
Rheumatoid arthritis (RA) is a chronic inflammatory disease that preferentially affects joints, and characterized by an approximately two-fold increased risk of cardiovascular diseases compared with the general population. Beyond classical cardiovascular risk factors, systemic inflammatory markers are primarily involved. Hence, anti-inflammatory strategies such as homocysteine-lowering interventions are warranted. Indeed, hyperhomocysteinemia is commonly found in RA patients as a result of both genetic and non-genetic factors including older age, male gender, disease-specific features and disease-modifying antirheumatic drugs. Most importantly in the pathophysiology of hyperhomocysteinemia and its related cardiovascular diseases in RA, there is a bi-directional link between immuno-inflammatory activation and hyperhomocysteinemia. As such, chronic immune activation causes B vitamins (including folic acid) depletion and subsequent hyperhomocysteinemia. In turn, hyperhomocysteinemia may perpetrate immuno-inflammatory stimulation via nuclear factor ƙappa B enhancement. This chronic immune activation is a key determinant of hyperhomocysteinemia-related cardiovascular diseases in RA patients. Folate, a homocysteine-lowering therapy could prove valuable for cardiovascular disease prevention in RA patients in the near future with respect to homocysteine reduction along with blockade of subsequent oxidative stress, lipid peroxidation, and endothelial dysfunction. Thus, large scale and long term homocysteine-lowering clinical trials would be helpful to clarify the association between hyperhomocysteinemia and cardiovascular diseases in RA patients and to definitely state conditions surrounding folic acid supplementation. This article reviews direct and indirect evidence for cardiovascular disease prevention with folic acid supplementation in RA patients.

No MeSH data available.


Related in: MedlinePlus

Homocysteine metabolism and major factors associated with hyperhomocysteinemia in rheumatoid arthritis patients. MTHFR methylene tetrahydrofolate; CBS cystathione β synthase; BHMT betaine homocysteine methyltransferase; MS methionine synthase; Vit vitamin; DMARDs disease-modifying antirheumatic drugs. Vit B9 depletion owing to immuno-inflammatory activation, DMARDs, and gastrointestinal disturbance impairs the MTHFR vit B9-dependent remethylation pathway together with the MTHFR C677T mutation; vit B12 depletion owing to both immuno-inflammatory activation and gastrointestinal disturbance impairs the MS vit B12-dependent remethylation pathway; vit B6 depletion owing to immuno-inflammatory activation and gastrointestinal disturbance impairs the CBS vit B6-dependent transsulfuration pathway
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Fig1: Homocysteine metabolism and major factors associated with hyperhomocysteinemia in rheumatoid arthritis patients. MTHFR methylene tetrahydrofolate; CBS cystathione β synthase; BHMT betaine homocysteine methyltransferase; MS methionine synthase; Vit vitamin; DMARDs disease-modifying antirheumatic drugs. Vit B9 depletion owing to immuno-inflammatory activation, DMARDs, and gastrointestinal disturbance impairs the MTHFR vit B9-dependent remethylation pathway together with the MTHFR C677T mutation; vit B12 depletion owing to both immuno-inflammatory activation and gastrointestinal disturbance impairs the MS vit B12-dependent remethylation pathway; vit B6 depletion owing to immuno-inflammatory activation and gastrointestinal disturbance impairs the CBS vit B6-dependent transsulfuration pathway

Mentions: HHcy is common among RA patients, as a consequence of both genetic and non-genetic factors associated with the disturbance of homocysteine metabolism [7–22]. Genetic risk factors are essentially represented by the methylenetetrahydrofolate reductase (MTHFR) 677C > T homozygous or heterozygous genotype which results in impaired homocysteine methylation to form methionine [8]. Whereas non-genetic factors include older age [9, 10], male gender [9, 10], RA-specific features [4, 7, 11–22], and disease-modifying antirheumatic drugs (DMARDs) [23–28] (Fig. 1).Fig. 1


Therapeutic potential of folic acid supplementation for cardiovascular disease prevention through homocysteine lowering and blockade in rheumatoid arthritis patients.

Essouma M, Noubiap JJ - Biomark Res (2015)

Homocysteine metabolism and major factors associated with hyperhomocysteinemia in rheumatoid arthritis patients. MTHFR methylene tetrahydrofolate; CBS cystathione β synthase; BHMT betaine homocysteine methyltransferase; MS methionine synthase; Vit vitamin; DMARDs disease-modifying antirheumatic drugs. Vit B9 depletion owing to immuno-inflammatory activation, DMARDs, and gastrointestinal disturbance impairs the MTHFR vit B9-dependent remethylation pathway together with the MTHFR C677T mutation; vit B12 depletion owing to both immuno-inflammatory activation and gastrointestinal disturbance impairs the MS vit B12-dependent remethylation pathway; vit B6 depletion owing to immuno-inflammatory activation and gastrointestinal disturbance impairs the CBS vit B6-dependent transsulfuration pathway
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4559887&req=5

Fig1: Homocysteine metabolism and major factors associated with hyperhomocysteinemia in rheumatoid arthritis patients. MTHFR methylene tetrahydrofolate; CBS cystathione β synthase; BHMT betaine homocysteine methyltransferase; MS methionine synthase; Vit vitamin; DMARDs disease-modifying antirheumatic drugs. Vit B9 depletion owing to immuno-inflammatory activation, DMARDs, and gastrointestinal disturbance impairs the MTHFR vit B9-dependent remethylation pathway together with the MTHFR C677T mutation; vit B12 depletion owing to both immuno-inflammatory activation and gastrointestinal disturbance impairs the MS vit B12-dependent remethylation pathway; vit B6 depletion owing to immuno-inflammatory activation and gastrointestinal disturbance impairs the CBS vit B6-dependent transsulfuration pathway
Mentions: HHcy is common among RA patients, as a consequence of both genetic and non-genetic factors associated with the disturbance of homocysteine metabolism [7–22]. Genetic risk factors are essentially represented by the methylenetetrahydrofolate reductase (MTHFR) 677C > T homozygous or heterozygous genotype which results in impaired homocysteine methylation to form methionine [8]. Whereas non-genetic factors include older age [9, 10], male gender [9, 10], RA-specific features [4, 7, 11–22], and disease-modifying antirheumatic drugs (DMARDs) [23–28] (Fig. 1).Fig. 1

Bottom Line: Rheumatoid arthritis (RA) is a chronic inflammatory disease that preferentially affects joints, and characterized by an approximately two-fold increased risk of cardiovascular diseases compared with the general population.Beyond classical cardiovascular risk factors, systemic inflammatory markers are primarily involved.Indeed, hyperhomocysteinemia is commonly found in RA patients as a result of both genetic and non-genetic factors including older age, male gender, disease-specific features and disease-modifying antirheumatic drugs.

View Article: PubMed Central - PubMed

Affiliation: Division of Medicine, Sangmelima Referral Hospital, P.O. Box 890, Sangmelima, Cameroon.

ABSTRACT
Rheumatoid arthritis (RA) is a chronic inflammatory disease that preferentially affects joints, and characterized by an approximately two-fold increased risk of cardiovascular diseases compared with the general population. Beyond classical cardiovascular risk factors, systemic inflammatory markers are primarily involved. Hence, anti-inflammatory strategies such as homocysteine-lowering interventions are warranted. Indeed, hyperhomocysteinemia is commonly found in RA patients as a result of both genetic and non-genetic factors including older age, male gender, disease-specific features and disease-modifying antirheumatic drugs. Most importantly in the pathophysiology of hyperhomocysteinemia and its related cardiovascular diseases in RA, there is a bi-directional link between immuno-inflammatory activation and hyperhomocysteinemia. As such, chronic immune activation causes B vitamins (including folic acid) depletion and subsequent hyperhomocysteinemia. In turn, hyperhomocysteinemia may perpetrate immuno-inflammatory stimulation via nuclear factor ƙappa B enhancement. This chronic immune activation is a key determinant of hyperhomocysteinemia-related cardiovascular diseases in RA patients. Folate, a homocysteine-lowering therapy could prove valuable for cardiovascular disease prevention in RA patients in the near future with respect to homocysteine reduction along with blockade of subsequent oxidative stress, lipid peroxidation, and endothelial dysfunction. Thus, large scale and long term homocysteine-lowering clinical trials would be helpful to clarify the association between hyperhomocysteinemia and cardiovascular diseases in RA patients and to definitely state conditions surrounding folic acid supplementation. This article reviews direct and indirect evidence for cardiovascular disease prevention with folic acid supplementation in RA patients.

No MeSH data available.


Related in: MedlinePlus