Genetically based hypertension generated through interaction of mild hypoalphalipoproteinemia and mild hyperhomocysteinemia

Carnicer, Ricardo; Navarro, María Á.; Arbonés-Mainar, José M.; Arnal, Carmen; Surra, Joaquín C.; Acı́n, Sergio; Sarría, Alfonso J.; Blanco‐Vaca, Francisco; Maeda, Nobuyo; Osada, Jesús

doi:10.1097/hjh.0b013e3281ab6c3d

Cited by 13 publications

(11 citation statements)

References 64 publications

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“…In the context of HHcy, an impaired antioxidant action of HDL could also be detrimental for endothelium relaxation through a decrease in nitric oxide availability [48]. Consistent with these data, the interaction of partial HDL deficiency and moderate HHcy in double heterozygous, apoA-I/CBS knockout mice concurred with a lower plasma nitric oxide concentration [34]. This suggests that the combination of both risk factors exacerbates endothelial dysfunction.…”

Section: Discussionmentioning

confidence: 61%

Methionine‐induced hyperhomocysteinemia impairs the antioxidant ability of high‐density lipoproteins without reducing in vivo macrophage‐specific reverse cholesterol transport

Julve

Escolà‐Gil

Rodríguez-Millán

et al. 2013

Molecular Nutrition Food Res

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Section: Discussionmentioning

confidence: 61%

Methionine‐induced hyperhomocysteinemia impairs the antioxidant ability of high‐density lipoproteins without reducing in vivo macrophage‐specific reverse cholesterol transport

Julve

Escolà‐Gil

Rodríguez-Millán

et al. 2013

Molecular Nutrition Food Res

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“…Therefore, our data suggest that this haplotype has a protective effect for hypertension. Indeed, the involvement of APOA1 in hypertension was recently demonstrated by Carnicer et al [48], using double heterozygous mice lacking one copy of CBS (cystathione b-synthase) and APOA1. These authors concluded that reduced levels of APOA1 combined with hyperhomocysteinemia could be related to the development of hypertension and cardiovascular abnormalities [48].…”

Section: Discussionmentioning

confidence: 93%

Apolipoprotein A1 gene polymorphisms as risk factors for hypertension and obesity

et al. 2009

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Several polymorphisms in apolipoprotein A1 (APOA1) gene have been associated with metabolic diseases. Increased transcription efficiency was observed in -75A allele carriers compared to -75G allele homozygotes. +83C allele was associated with higher body mass index and waist-to-hip ratio in type II diabetes subjects. -75G/A and +83C/T polymorphisms were analyzed by RFLP-PCR in 334 individuals from a Brazilian elderly cohort. APOA1 polymorphisms were associated with age-related morbidities, as well as with triglycerides, total cholesterol, HDL, VLDL, LDL, creatinine, urea, albumin, glycated hemoglobin and fasting glucose serum levels. Allele frequencies were 0.102 and 0.21, respectively, for -75A and +83T. -75G allele showed significant association with hypertension (P = 0.001). An association between +83C allele and obesity was observed (P = 0.040) and this allele also showed an association with hypertension in the presence of cardiovascular disease (P = 0.047). Moreover, +83T allele was associated with lower glycated hemoglobin values (P = 0.026). To our knowledge, there is no data associating this polymorphism with glycated hemoglobin. Furthermore, individuals carrying AT haplotype have lower risk for developing hypertension (P = 0.0002), while GT haplotype carriers present decreased risk to develop obesity comparing to GC haplotype (P = 0.025). APOA1 polymorphisms analysis may be a useful tool to identify risk factors for subjects and families and clarify the physiopathological role of these polymorphisms in age-related diseases, such as hypertension and obesity.

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“…ApoA1 is the major protein constituent of HDL and is responsible for HDL's cardiovascular-protective properties of promoting cholesterol efflux from tissues to the liver for excretion. Double heterozygous cbs ϩ/Ϫ ApoA1 ϩ/Ϫ mice develop hypertension compared with WT mice (aorta systolic pressure: 124 Ϯ 7.7 vs. 109 Ϯ 11.2 mmHg, P Ͻ 0.05) and cardiac muscle hypertrophy (20,21). Simvastatin, a statin-class drug commonly used to treat hypercholesterolemia and CVD, restored systolic pressure to control values and significantly lowered plasma [Hcy] (5.8 Ϯ 0.8 vs. 4.9 Ϯ 0.7 M, P Ͻ 0.05) (22); these effects were independent of plasma lipids but related to increased NO production.…”

Section: Dyslipidosis Thrombosis and Arteriosclerosis In Cbs Deficimentioning

confidence: 98%

Vascular complications of cystathionine β-synthase deficiency: future directions for homocysteine-to-hydrogen sulfide research

Beard

Bearden

2011

American Journal of Physiology-Heart and Circulatory Physiology

106

110

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Homocysteine (Hcy), a cardiovascular and neurovascular disease risk factor, is converted to hydrogen sulfide (H(2)S) through the transsulfuration pathway. H(2)S has attracted considerable attention in recent years for many positive effects on vascular health and homeostasis. Cystathionine β-synthase (CBS) is the first, and rate-limiting, enzyme in the transsulfuration pathway. Mutations in the CBS gene decrease enzymatic activity, which increases the plasma Hcy concentration, a condition called hyperhomocysteinemia (HHcy). Animal models of CBS deficiency have provided invaluable insights into the pathological effects of transsulfuration impairment and of both mild and severe HHcy. However, studies have also highlighted the complexity of HHcy and the need to explore the specific details of Hcy metabolism in addition to Hcy levels per se. There has been a relative paucity of work addressing the dysfunctional H(2)S production in CBS deficiency that may contribute to, or even create, HHcy-associated pathologies. Experiments using CBS knockout mice, both homozygous (-/-) and heterozygous (+/-), have provided 15 years of new knowledge and are the focus of this review. These murine models present the opportunity to study a specific mechanism for HHcy that matches one of the etiologies in many human patients. Therefore, the goal of this review was to integrate and highlight the critical information gained thus far from models of CBS deficiency and draw attention to critical gaps in knowledge, with particular emphasis on the modulation of H(2)S metabolism. We include findings from human and animal studies to identify important opportunities for future investigation that should be aimed at generating new basic and clinical understanding of the role of CBS and transsulfuration in cardiovascular and neurovascular disease.

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Genetically based hypertension generated through interaction of mild hypoalphalipoproteinemia and mild hyperhomocysteinemia

Abstract: Our findings suggest an additive adverse effect of hypoalphalipoproteinemia and hyperhomocysteinemia on endothelial function to generate clinical hypertension and cardiac muscle hypertrophy mediated by dysregulation in nitric oxide metabolism.

Cited by 13 publications

References 64 publications

Methionine‐induced hyperhomocysteinemia impairs the antioxidant ability of high‐density lipoproteins without reducing in vivo macrophage‐specific reverse cholesterol transport

Methionine‐induced hyperhomocysteinemia impairs the antioxidant ability of high‐density lipoproteins without reducing in vivo macrophage‐specific reverse cholesterol transport

Apolipoprotein A1 gene polymorphisms as risk factors for hypertension and obesity

Vascular complications of cystathionine β-synthase deficiency: future directions for homocysteine-to-hydrogen sulfide research

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