Angiotensin II Type 1 Receptor Gene Polymorphism Is Associated with an Increased Vascular Reactivity in the Human Mammary Artery in vitro

Henrion, Didier; Amant, Carole; Bénessiano, Joëlle; Philip, Ivan; Plantefève, Gaëtan; Chatel, Didier; Hwas, Ulrich; Desmont, J.M.; Durand, Geneviève; Amouyel, Philippe; Lévy, Bernard

doi:10.1159/000025605

Cited by 48 publications

(33 citation statements)

References 16 publications

(39 reference statements)

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“…75 In vivo and in vitro studies of human arterial rings have shown that the constrictive effects of angiotensin II and phenylephrine are significantly amplified by comparison with the other genotype subgroups. 76 Finally, in hypertensive populations, subjects with AT 1 receptor gene polymorphism exhibit a greater pressure-independent decrease in aortic stiffness than the other genotypic subgroup for the same degree of convertingenzyme inhibition, whereas a comparable effect is not observed with calcium-entry blockade. 77 …”

Section: Stiffness Changes Associated With Sodium and Renin-angiotensmentioning

confidence: 98%

Pulse Pressure, Arterial Stiffness, and Drug Treatment of Hypertension

2001

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Abstract-Epidemiological studies in the past decade have stressed the importance of pulse pressure as an independent risk factor for cardiovascular morbidity and mortality. We briefly review the epidemiological evidence and discuss in more detail the pathophysiological basis for this observation and the therapeutic consequences. We focus on the vascular determinants of increased pulse pressure. Both longitudinal and cross-sectional components of the vascular system contribute to the shape of the arterial pressure wave and, thereby, to pulse pressure. The primary longitudinal component is the architecture of the arterial tree, which determines the major reflection sites for the pressure wave. The cross-sectional architecture of the vascular system consists of a geometric (diameter) and a structural (composition vessel wall) component. Both diameter and composition of the vessel wall vary greatly when going from central to more peripheral arteries. We review the implications for the functional properties of various arterial segments. Finally, we discuss the therapeutic consequences of targeting pulse pressure rather than mean blood pressure with various drug classes. Among the antihypertensive agents, nitrates, NO donors, and drugs that interfere with the renin-angiotensinaldosterone system may offer useful tools to lower pulse pressure, in addition to mean blood pressure. Future developments may include non-antihypertensive agents that target collagen or other components of the arterial wall matrix. However, large-scale clinical trials will have to confirm the therapeutic value of these agents in the treatment of increased pulse pressure and arterial stiffness. Key Words: antihypertensive agents Ⅲ arterial stiffness Ⅲ epidemiology Ⅲ pulse pressure Ⅲ blood pressure H ypertension is a cardiovascular (CV) risk factor, the mechanisms of which are generally attributed to the reduction in the caliber or number of small arteries or arterioles with a resulting increase in total peripheral resistance and mean blood pressure (MBP). MBP, the product of cardiac output and total peripheral resistance, refers to steady phenomena, considering pressure and flow as constant over time. This definition does not take into account that blood pressure and flow fluctuate during the cardiac cycle. In clinical practice, pressure is defined in terms of systolic (SBP) and diastolic (DBP) blood pressure, which refer to a pulsatile phenomenon, with SBP and DBP representing the extremes of the blood pressure oscillation around a mean value, the MBP. In fact, the blood pressure curve may be considered as the summation of a steady component, MBP, and a pulsatile component, the pulse pressure (PP). 1 Besides the pattern of left ventricular ejection, the determinants of PP (and SBP) are the cushioning capacity (compliance) of arteries and the timing and intensity of arterial wave reflections. 1 Compliance of arteries depends on arterial volume and the elastic properties (distensibility) of arterial walls. Compliance and distensibility are quantit...

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Section: Stiffness Changes Associated With Sodium and Renin-angiotensmentioning

confidence: 98%

Pulse Pressure, Arterial Stiffness, and Drug Treatment of Hypertension

2001

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“…In this study, we have tested the hypothesis that genetic variations in the egfr gene shared between normal and malignant tumors could explain the observed clinical association. Several studies have revealed that polymorphic variations in genes encoding drug targets affect the response and toxicity to therapeutic agents (17)(18)(19)(20)(21)(22). The egff gene contains a highly polymorphic sequence in intron 1, which consists of a variable number of CA dinucleotide repeats ranging from 9 to 21 (23).…”

Section: Introductionmentioning

confidence: 99%

An Epidermal Growth Factor Receptor Intron 1 Polymorphism Mediates Response to Epidermal Growth Factor Receptor Inhibitors

et al. 2004

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This study tested the hypothesis that the number of CA single sequence repeat (CA-SSR) in the intron 1 of the epidermal growth factor receptor (egfr) gene, which affects transcription efficiency of the gene, is associated with the response to EGFR inhibitors. To this end, we determined the number of CA dinucleotides in the intron 1 of the egfr gene in a panel of 12 head and neck cancer cell lines that lack egfr gene amplification and measured the expression of EGFR (mRNA and protein), as well as response to EGFR inhibition. Cells with lower number of CA dinucleotides in the CA-SSR had higher expression of the EGFR gene and protein and were more sensitive to the inhibitory effects of erlotinib, a small molecule inhibitor of the EGFR tyrosine-kinase. Phenotypic modification by silencing EGFR mRNA expression in a susceptible cell line induced resistance to the drug. The number of CA dinucleotide was equivalent in genomic and tumor DNA obtained from 30 patients with head and neck cancer. In a clinical study in colorectal cancer, subjects with lower number of CA dinucleotide frequently developed skin toxicity, a feature that is related to the antitumor activity of this class of drugs. These results suggest that polymorphic variations in the intron 1 of the egfr gene is associated with response to EGFR inhibitors and may provide an explanation as to why the development of skin toxicity is associated with a favorable outcome in patients treated with these agents.

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“…5 Some examples include polymorphisms in the b2-adrenoreceptors and sensitivity to b2-agonists in asthmatics, 6 polymorphisms in neurotransmitter-receptor-related genes and response to clozaphine in schizophrenic patients, 7 and polymorphisms in angiotensin II T1 receptor and vascular reactivity to phenylephrine. 8 The type 1 interferons, which include about 15 cytokines (13 isotypes of IFNa, one IFNb, one IFNo), all share the same receptor, IFNAR, for binding. 9 The two subunits of the receptor, IFNAR1 and IFNAR2, are coded by two different genes located close to each other on chromosome 21q22.1.…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenomic analysis of interferon receptor polymorphisms in multiple sclerosis

et al. 2003

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Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system characterized by progressive neurological dysfunction. No curative therapy is currently available, and approximately 80-90% of afflicted individuals are ultimately disabled. Interferon beta (IFNb) has been shown to decrease clinical relapses, reduce brain disease activity, and possibly slow progression of disability. However, the overall effect of treatment is partial and a substantial number of patients are considered poor or nonresponders. For this report, we tested the pharmacogenomic effects of eight polymorphisms in the interferon receptor genes (IFNAR1 and IFNAR2) in a group of 147 patients undergoing open-label IFNb therapy. Overall, no significant differences in the distribution of responders and nonresponders, classified based on prospectively acquired primary and secondary clinical end points, were observed when stratified by any of the studied IFNAR gene polymorphisms. A trend detected with a single nucleotide polymorphism SNP 16469 (A/T) located at the third intron of the IFNAR1 gene, suggesting modest association with relapse-free status, will require confirmation in an independent data set. In addition, no significant association was observed of any of the IFNAR gene polymorphisms with susceptibility to MS, as studied by a family-based association analysis.

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Angiotensin II Type 1 Receptor Gene Polymorphism Is Associated with an Increased Vascular Reactivity in the Human Mammary Artery in vitro

Cited by 48 publications

References 16 publications

Pulse Pressure, Arterial Stiffness, and Drug Treatment of Hypertension

Pulse Pressure, Arterial Stiffness, and Drug Treatment of Hypertension

An Epidermal Growth Factor Receptor Intron 1 Polymorphism Mediates Response to Epidermal Growth Factor Receptor Inhibitors

Pharmacogenomic analysis of interferon receptor polymorphisms in multiple sclerosis

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