Genetic Risk of Primary Aldosteronism and Its Contribution to Hypertension: A Cross-Ancestry Meta-Analysis of Genome-Wide Association Studies.

Background: Hypertension imposes substantial health and economic burden worldwide. Primary aldosteronism (PA) is one of the most common causes of secondary hypertension, causing cardiovascular events at higher risk compared with essential hypertension. However, the germline genetic contribution to the susceptibility of PA has not been well elucidated.

Association of DNA methylation with steroidogenic enzymes in Cushing's adenoma.

DNA methylation and demethylation regulate the transcription of genes. DNA methylation-associated gene expression of adrenal steroidogenic enzymes may regulate cortisol production in cortisol-producing adenoma (CPA). We aimed to determine the DNA methylation levels of all genes encoding steroidogenic enzymes involved in CPA.

Hypomethylation associated vitamin D receptor expression in ATP1A1 mutant aldosterone-producing adenoma.

DNA methylation alteration is tissue-specific and play a pivotal role in regulating gene transcription during cell proliferation and survival. We aimed to detect genes regulated by DNA methylation, and then investigated whether the gene influenced cell proliferation or survival in adrenal cells. DNA methylation and qPCR analyses were performed in nonfunctioning adrenocortical adenoma (NFA, n = 12) and aldosterone-producing adenoma (APA, n = 35) samples.

Mutant in Aldosterone-Producing Adenoma Leads to Cell Proliferation.

The molecular mechanisms by which mutation-mediated cell proliferation or tumorigenesis in aldosterone-producing adenomas (APAs) have not been elucidated. First, we investigated whether the APA-associated L104R mutation stimulated cell proliferation. Second, we aimed to clarify the molecular mechanisms by which the mutation-mediated cell proliferated.

Genotype-specific cortisol production associated with Cushing's syndrome adenoma with PRKACA mutations.

The intracellular molecular mechanisms underlying the genotype of cortisol-producing adenoma (CPA) have not been fully determined. We analyzed gene expressions in CPA and the human adrenocortical cell line (HAC15 cells) with PRKACA mutation. Clustering analysis using a gene set associated with responses to cAMP revealed the possible differences between PRKACA mutant CPAs and GNAS and CTNNB1 mutant CPAs.

Angiotensin-converting enzyme 2 expression is not induced by the renin-angiotensin system in the lung.

https://bit.ly/3fkopuO.

Long-term effects of non-retrieved inferior vena cava filters on recurrences of venous thromboembolism in cancer and non-cancer patients: From the COMMAND VTE registry.

Background: There is a paucity of data comparing the long-term outcomes after inferior vena cava (IVC) filters placement for patients with acute venous thromboembolism (VTE) between those with and without active cancer.

Methods: In the COMMAND VTE Registry, we evaluated the effects of IVC filter use on the long-term clinical outcomes stratified by the presence and absence of active cancer.

Results: Among 2,626 patients with acute symptomatic VTE, there were 604 patients with active cancer, and 2022 patients without active cancer.

Variation in plasma glucagon levels according to obesity status in Japanese Americans with normal glucose tolerance.

Japanese Americans living in the United States are genetically identical to Japanese people, but have undergone a rapid and intense westernization of their lifestyle. This study investigated variability in glucagon secretion after glucose loading among Japanese Americans with normal glucose tolerance (NGT) according to obesity status. The 75-g oral glucose tolerance test (OGTT) was performed for 138 Japanese Americans (aged 40-75 years) living in Los Angeles.

Retrograde-angioscopy guided wiring technique in chronic total occlusion lead to successful revascularization.

Endovascular therapy (EVT) was performed in two cases with chronic total occlusion (CTO) of superficial femoral artery. In these cases, angioscopy was deployed in the backyard of the CTO lesion from popliteal artery retrogradely, then the guidewire was advanced from antegrade. When the wire crossed the distal of the CTO lesion, the wire penetration was clearly visualized by the retrograde-angioscopy.

Predictive value of the coronary artery calcium score and advanced plaque characteristics: Post hoc analysis of the PREDICT registry.

Background: Whether coronary plaque characteristics assessed in coronary computed tomography angiography (CCTA) in association with the coronary artery calcium score (CACS) have predictive value for coronary events is unclear. We aimed to examine the predictive value of the CACS and plaque characteristics for the occurrence of coronary events.

Methods: Among 2802 patients who were analyzed in the PREDICT registry, 2083 with suspected coronary artery disease (CAD) were studied using post hoc analysis.

Determinants and prognostic implications of instantaneous wave-free ratio in patients with mild to intermediate coronary stenosis: Comparison with those of fractional flow reserve.

The instantaneous wave-free ratio (iFR) is used for assessing the hemodynamic severity of a lesion, as an alternative to the fractional flow reserve (FFR). We evaluated the relationship between iFR and FFR in detail and the clinical significance of iFR in patients with mild to intermediate coronary artery stenosis. We recruited consecutive 323 patients (421 lesions) with lesions exhibiting 30% to 80% diameter stenosis on angiography in whom FFR and iFR were measured.

Investigations of an inducible intact dystrophin gene excision system in cardiac and skeletal muscle in vivo.

We sought here to induce the excision of a large intragenic segment within the intact dystrophin gene locus, with the ultimate goal to elucidate dystrophin protein function and stability in striated muscles in vivo. To this end, we implemented an inducible-gene excision methodology using a floxed allele approach, demarcated by dystrophin exons 2-79, in complementation with a cardiac and skeletal muscle directed gene deletion system for spatial-temporal control of dystrophin gene excision in vivo. Main findings of this study include evidence of significant intact dystrophin gene excision, ranging from ~ 25% in heart muscle to ~ 30-35% in skeletal muscles in vivo.

A 50-year history of the health impacts of Westernization on the lifestyle of Japanese Americans: A focus on the Hawaii-Los Angeles-Hiroshima Study.

A medical survey of Japanese Americans have been carried out since 1970; in particular, this survey was administered to the Japanese emigrants from Hiroshima (Japan) to Hawaii or Los Angeles (USA) and their offspring. Labeled the Hawaii-Los Angeles-Hiroshima Study, it constituted a long-term epidemiological study of Japanese Americans who are genetically identical to the native Japanese people, but have experienced rapid and intense Westernization in terms of their lifestyles. The authors have compared the medical survey data procured from two Japanese populations, evincing very disparate lifestyles; that is, the native Japanese inhabitants of Hiroshima (Japan) and Japanese Americans living in Hawaii or Los Angeles (USA).

Right ventricular involvement is an important prognostic factor and risk stratification tool in suspected cardiac sarcoidosis: analysis by cardiac magnetic resonance imaging.

Background: Late gadolinium enhancement imaging (LGE) of the left ventricle (LV) by cardiac magnetic resonance (CMR) has prognostic value for patients with cardiac sarcoidosis (CS). Right ventricle (RV) dysfunction is also associated with adverse outcomes in patients with heart failure. Therefore, we sought to determine if RV LGE and dysfunction predicted adverse events in patients with suspected CS.

Endoplasmic Reticulum Chaperone Calmegin Is Upregulated in Aldosterone-Producing Adenoma and Associates With Aldosterone Production.

The endoplasmic reticulum (ER) plays a pivotal role in syntheses of proteins and steroid hormones and regulation of intracellular Ca level. We aimed to investigate ER-associated genes in aldosterone-producing adenomas (APAs) and clarify their effect on aldosterone production. Microarray analysis targeting 288 ER-associated genes was conducted using nonfunctioning adrenocortical adenomas (n=5) and APAs (n=19).

Associations of nutrient intakes with glaucoma among Japanese Americans.

The aim of this study was to investigate possible associations of nutrient intake on glaucoma in subjects of Japanese descent living in Los Angeles, CA.In this cross-sectional study, 581 Japanese American participants in Los Angeles underwent an interview, fundus photography, comprehensive physical, and blood examinations, along with determining the body mass index status and any confounding factors. CDSketch was used to measure the cup-disc ratio and rim width of each fundus in the retinal photographs.

Alteration of gut microbiota by a Westernized lifestyle and its correlation with insulin resistance in non-diabetic Japanese men.

Aims/introduction: The severity of insulin resistance is higher in Japanese-American people with American lifestyles than in native Japanese people with Japanese lifestyles. Recently, the role of gut microbiota in the control of host metabolic homeostasis and organ physiology has been recognized. In addition, gut microbiota alterations have been suggested to contribute to pathogenesis of insulin resistance.

Measurement of midnight ACTH levels is useful for the evaluation of midnight cortisol levels.

Objective: Elevated midnight cortisol levels induced by non-suppressed ACTH levels may lead to false-positive results for hypercortisolism in patients with adrenal incidentaloma. We investigated whether plasma ACTH-associated high midnight serum cortisol levels are correlated with other endocrinological findings with respect to hypothalamic-pituitaryadrenal function or hypercortisolism status.

Methods: Two-hundred-forty-six patients with adrenocortical adenoma were evaluated via measurements of midnight ACTH and cortisol levels, a 1-mg dexamethasone suppression test (DST), and a cosyntropin-releasing hormone (CRH) stimulation test.

Angiotensin 1-7 suppresses angiotensin II mediated aldosterone production via JAK/STAT signaling inhibition.

Angiotensin 1-7 (Ang 1-7), which is a protein cleaved from angiotensin II (A-II), binds to the MAS receptor. Ang 1-7 has been demonstrated to exert protective effects against A-II-mediated cardiac, atherosclerotic, and renal damages. The aims of our study were to demonstrate the inhibitory role of Ang 1-7 in A-II-mediated aldosterone production by interacting with the MAS receptor in human adrenocortical carcinoma (HAC15) cells, and clarify the intracellular signaling mechanisms underlying the inhibition of aldosterone production by Ang 1-7.

Coronary plaque characteristics in computed tomography and 2-year outcomes: The PREDICT study.

Background: Coronary computed tomography angiography (CCTA) not only provides information regarding luminal stenoses but also allows for visualization of mural atheromatous changes (coronary plaques).

Objective: We sought to elucidate whether plaques seen on CCTA enable prediction of 2-year outcomes in patients with suspected and known coronary artery disease (CAD).

Methods: Of 3015 patients who underwent CCTA, the images and 2-year clinical courses of 2802 patients were independently analyzed.

Purkinje Cell Protein 4 Expression Is Associated With DNA Methylation Status in Aldosterone-Producing Adenoma.

Context: Aldosterone production is stimulated by activation of calcium signaling in aldosterone-producing adenomas (APAs), and epigenetic factors such as DNA methylation may be associated with the expression of genes involved in aldosterone regulation.

Objective: Our aim was to investigate the DNA methylation of genes related to calcium signaling cascades in APAs and the association of mutations in genes linked to APAs with DNA methylation levels.

Methods: Nonfunctioning adrenocortical adenoma (n = 12) and APA (n = 35) samples were analyzed.