Association Study of the Elastin Microfibril Interfacer 1 (EMILIN1) Gene in Essential Hypertension

Shimodaira, Masanori; Nakayama, Tomohiro; Sato, Naoyuki; Naganuma, Takahiro; Yamaguchi, Mai; Aoi, Noriko; Sato, Mitsugu; Izumi, Yasukatsu; Soma, Masayoshi; Matsumoto, Koichí

doi:10.1038/ajh.2010.16

Cited by 25 publications

(18 citation statements)

References 26 publications

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“…Cry1/2 −/− mice show elevated transcription and enhanced enzymatic activity of type VI 3β-hydroxyl-steroid dehydrogenase (Hsd3b6), which is expressed exclusively in aldosterone-producing cells under transcriptional control of the circadian clock. Moreover, single-nucleotide polymorphisms in the HSD3B1 gene, the human ortholog of Hsd3b6, are associated with elevated systolic and diastolic blood pressure and plasma aldosterone activity (Rosmond et al, 2002;Shimodaira et al, 2010). Moreover, single-nucleotide polymorphisms in the HSD3B1 gene, the human ortholog of Hsd3b6, are associated with elevated systolic and diastolic blood pressure and plasma aldosterone activity (Rosmond et al, 2002;Shimodaira et al, 2010).…”

Section: (B) Circadian Regulation Of Gc Action Prior To Binding To Gmentioning

confidence: 99%

Adrenal Clocks and the Role of Adrenal Hormones in the Regulation of Circadian Physiology

et al. 2014

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The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) and subordinate clocks that disseminate time information to various central and peripheral tissues. While the function of the SCN in circadian rhythm regulation has been extensively studied, we still have limited understanding of how peripheral tissue clock function contributes to the regulation of physiological processes. The adrenal gland plays a special role in this context as adrenal hormones show strong circadian secretion rhythms affecting downstream physiological processes. At the same time, they have been shown to affect clock gene expression in various other tissues, thus mediating systemic entrainment to external zeitgebers and promoting internal circadian alignment. In this review, we discuss the function of circadian clocks in the adrenal gland, how they are reset by the SCN and may further relay time-of-day information to other tissues. Focusing on glucocorticoids, we conclude by outlining the impact of adrenal rhythm disruption on neuropsychiatric, metabolic, immune, and malignant disorders.

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Section: (B) Circadian Regulation Of Gc Action Prior To Binding To Gmentioning

confidence: 99%

Adrenal Clocks and the Role of Adrenal Hormones in the Regulation of Circadian Physiology

et al. 2014

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“…In fact, recent association studies have suggested that specific haplotypes of EMILIN1 are useful genetic markers of essential hypertension in Japanese men and that the interaction of age and genotype variation of specific single nucleotide polymorphisms might increase the risk of hypertension in a northern Han Chinese population. 6,7 Here, we have addressed the question of the cellular context of Emilin-1 activity using a phenotype rescue approach by expressing the protein in either ECs or VSMCs or in all cells of the arterial wall of Emilin1 −/− mice. Our results indicate that Emilin-1 expression in VSMCs is specifically required for BP control and further clarify that the protein regulates the arteriolar myogenic response through TGF-β.…”

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confidence: 99%

Vascular Smooth Muscle Emilin-1 Is a Regulator of Arteriolar Myogenic Response and Blood Pressure

Litteri

Carnevale

D’Urso

et al. 2012

ATVB

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Objective-Emilin-1 is a protein of elastic extracellular matrix involved in blood pressure (BP) control by negatively affecting transforming growth factor (TGF)-β processing. Emilin1 null mice are hypertensive. This study investigates how Emilin-1 deals with vascular mechanisms regulating BP. Methods and Results-This study uses a phenotype rescue approach in which Emilin-1 is expressed in either endothelial cells or vascular smooth muscle cells of transgenic animals with the Emilin1 −/− background. We found that normalization of BP required Emilin-1 expression in smooth muscle cells, whereas expression of the protein in endothelial cells did not modify the hypertensive phenotype of Emilin1 −/− mice. We also explored the effect of treatment with anti-TGF-β antibodies on the hypertensive phenotype of Emilin1 −/− mice, finding that neutralization of TGF-β in Emilin1 null mice normalized BP quite rapidly (2 weeks). Finally, we evaluated the vasoconstriction response of resistance arteries to perfusion pressure and neurohumoral agents in different transgenic mouse lines. Interestingly, we found that the hypertensive phenotype was coupled with an increased arteriolar myogenic response to perfusion pressure, while the vasoconstriction induced by neurohumoral agents remained unaffected. We further elucidate that, as for the hypertensive phenotype, the increased myogenic response was attributable to increased TGF-β activity. Key Words: Emilin1 ◼ myogenic response ◼ systemic hypertension ◼ transforming growth factor ◼ vascular smooth muscle Conclusion-Our

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“…Many candidate genes have been reported to be involved in essential hypertension susceptibility, including TSC, NEDD4L (Luo et al, 2009), CYP4F2 (Ward et al, 2008), EMILIN 1 (Shimodaira et al, 2010), ATP2B1 (Tabara et al, 2010), apelin-AGTRL1 system (Niu et al, 2010), and so on. Several studies suggest that TSC plays a major role in sodium and chloride re-absorption in the distal convoluted tubule, accounting for a significant proportion of the total renal sodium re-absorption (Plotkin et al, 1996;Matsuo et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Lack of an association between TSC gene Arg904Gln polymorphisms and essential hypertension risk based on a meta-analysis

Zhang¹,

Yang²,

Hu³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. Although there have been several studies investigating a possible association between essential hypertension and TSC gene Arg904Gln polymorphisms, the results have been inconsistent. We conducted a meta-analysis of four case-control studies (one study in Europe and three studies in Asia), including 1811 essential hypertension cases and 1381 controls. The pooled results showed no significant associations between any of these polymorphisms and essential hypertension (allele Arg vs allele Gln: odds ratio (OR) = 0.94, 95% confidence interval (95%CI) = 0.70-1.27), additive genetic model (Arg/Arg vs Gln/Gln: OR = 0.98, 95%CI = 0.43-2.23), dominant genetic model (Arg/Arg + Arg/Gln vs Gln/ Gln: OR = 0.97, 95%CI = 0.43-2.21), and recessive genetic model (Arg/ Arg vs Arg/Gln + Gln/Gln: OR = 1.03, 95%CI = 0.45-2.35). Based on the results of our meta-analysis, we conclude that the TSC gene Arg904Gln polymorphism is not associated with essential hypertension risk.

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Association Study of the Elastin Microfibril Interfacer 1 (EMILIN1) Gene in Essential Hypertension

Abstract: We confirmed that rs2289360, rs2011616, and rs2304682 in the human EMILIN1 gene, as well as the haplotype constructed using rs2536512, rs2011616, and rs17881426 are useful genetic markers of EH in Japanese men.

Cited by 25 publications

References 26 publications

Adrenal Clocks and the Role of Adrenal Hormones in the Regulation of Circadian Physiology

Adrenal Clocks and the Role of Adrenal Hormones in the Regulation of Circadian Physiology

Vascular Smooth Muscle Emilin-1 Is a Regulator of Arteriolar Myogenic Response and Blood Pressure

Lack of an association between TSC gene Arg904Gln polymorphisms and essential hypertension risk based on a meta-analysis

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