0000000000180110
AUTHOR
John C. Burnett
The Atrial Natriuretic Peptide Genetic Variant rs5068 Is Associated With a Favorable Cardiometabolic Phenotype in a Mediterranean Population
OBJECTIVE We hypothesized that the minor allele of the atrial natriuretic peptide (ANP) genetic variant rs5068 is associated with a favorable cardiometabolic phenotype in a general Mediterranean population. RESEARCH DESIGN AND METHODS We genotyped a random sample of the residents of Ventimiglia di Sicilia, Sicily, for rs5068. RESULTS Genotype frequencies of rs5068 are AA, 93.5%; AG, 6.4%; and GG, 0.1%. All subsequent analyses are AA versus AG+GG. After adjusting for age and sex, the minor G allele is associated with lower BMI (estimate [SE]: −1.7 kg/m2 [0.8], P = 0.04). In the AG+GG group, males with HDL cholesterol levels <40 mg/dL are less frequent (P = 0.05) and obesity tends to …
The aging heart, myocardial fibrosis, and its relationship to circulating C-type natriuretic Peptide.
Myocardial aging is characterized by left ventricular (LV) fibrosis leading to diastolic and systolic dysfunction. Studies have established the potent antifibrotic and antiproliferative properties of C-type natriuretic peptide (CNP); however, the relationship between circulating CNP, LV fibrosis, and associated changes in LV function with natural aging are undefined. Accordingly, we characterized the relationship of plasma CNP with LV fibrosis and function in 2-, 11-, and 20-month–old male Fischer rats. Further in vitro, we established the antiproliferative actions of CNP and the participation of the clearance receptor using adult human cardiac fibroblasts. Here we establish for the first t…
The ANP Genetic Variant RS5068 is Associated With a Favorable Cardiometabolic Phenotype in a Mediterranean Population
Introduction: Atrial natriuretic peptide (ANP) possesses cardiorenal protective properties including natriuresis, aldosterone suppression and vasodilation. Importantly, ANP also exerts lipolytic effects in vitro and in vivo. Previous studies reported that the ANP genetic variant rs5068 is associated with increased plasma levels of ANP, lower blood pressure values, and reduced risk of hypertension. We recently reported that in a random sample of the general population from Olmsted County, MN the G allele of rs5068 was associated with increased levels of ANP, lower blood pressure and BMI, waist circumference, reduced prevalence of obesity and metabolic syndrome. To date, these associations ha…
A genetic variant of the atrial natriuretic peptide gene is associated with cardiometabolic protection in the general community
Objectives We sought to define the cardiometabolic phenotype associated with rs5068, a genetic variant of the atrial natriuretic peptide (ANP) gene. Background The ANP and B-type natriuretic peptide play an important role in cardiorenal homeostasis but also exert metabolic actions. Methods We genotyped 1,608 randomly selected residents from Olmsted County, Minnesota. Subjects were well-characterized. Results Genotype frequencies were: AA 89.9%, AG 9.7%, and GG 0.4%; all subsequent analyses were AA versus AG+GG. The G allele was associated with increased plasma levels of N-terminal pro-atrial natriuretic peptide (p = 0.002), after adjustment for age and sex. The minor allele was also associa…
Long-Term Structural and Functional Myocardial Adaptations in Healthy Living Kidney Donors: A Pilot Study
Background and Aims Compensatory renal hypertrophy following unilateral nephrectomy (UNX) occurs in the remaining kidney. However, the long-Term cardiac adaptive process to UNX remains poorly defined in humans. Our goal was to characterize myocardial structure and function in living kidney donors (LKDs), approximately 12 years after UNX. Methods and Results Cardiac function and structure in 15 Italian LKDs, at least 5 years after UNX (median time from donation = 8.4 years) was investigated and compared to those of age and sex matched U.S. citizens healthy controls (n = 15). Standard and speckle tracking echocardiography (STE) was performed in both LKDs and controls. Plasma angiotensin II, a…
Human Hypertension Is Characterized by a Lack of Activation of the Antihypertensive Cardiac Hormones ANP and BNP
ObjectivesThis study sought to investigate plasma levels of circulating cardiac natriuretic peptides, atrial natriuretic peptide (ANP) and B-type or brain natriuretic peptide (BNP), in the general community, focusing on their relative differences in worsening human hypertension.BackgroundAlthough ANP and BNP are well-characterized regulators of blood pressure in humans, little is known at the population level about their relationship with hypertension. The authors hypothesized that hypertension is associated with a lack of activation of these hormones or their molecular precursors.MethodsThe study cohort (N = 2,082, age >45 years) was derived from a random sample from Rochester, Minnesota, …
Long-term cardiac pro-B-type natriuretic peptide gene delivery prevents the development of hypertensive heart disease in spontaneously hypertensive rats.
Background— Diastolic dysfunction associated with high blood pressure (BP) leads to cardiac remodeling and fibrosis and progression to congestive heart failure. B-type natriuretic peptide (BNP) has BP-lowering, antifibrotic, and antihypertrophic properties, which makes BNP an attractive agent for attenuating the adverse cardiac remodeling associated with hypertension. In the current study, we tested the effects of sustained cardiac proBNP gene delivery on BP, cardiac function, and remodeling in spontaneously hypertensive rats (SHR). Methods and Results— We used the myocardium-tropic adeno-associated virus serotype 9 (AAV9) vector to achieve continuously enhanced cardiac rat proBNP expressi…
Genetic variants of ANP and cardiometabolic protection: from populations to novel therapeutics
Background The cardiac hormone atrial natriuretic peptide (ANP) induces natriuresis, vasodilation and inhibits aldosterone through the activation of the guanylyl cyclase A receptor (GC-A) and the second messenger cGMP. ANP possesses also metabolic properties enhancing lipolysis and release of the adipokine adiponectin. Previous studies in general populations reported that the minor G allele of the ANP genetic variant rs5068 is associated with increased circulating levels of ANP and B-type natriuretic peptide, lower blood pressure (BP), and reduced risk of hypertension. We recently reported that in the general population from Olmsted County, MN, USA the G allele of rs5068 is associated not o…
Cardiac Micro–Computed Tomography Imaging of the Aging Coronary Vasculature
Background— Alterations at the level of the coronary circulation with aging may play an important role in the evolution of age-associated changes in left ventricular (LV) fibrosis and function. However these age-associated changes in the coronary vasculature remain poorly defined primarily due to the lack of high resolution imaging technologies. The current study was designed to utilize cardiac micro–computed tomography (micro-CT) technology as a novel imaging strategy, to define the 3-dimensional coronary circulation in the young and aged heart and its relationship to LV fibrosis and function. Methods and Results— Young (2 months old; n=10) and aged (20 months old; n=10) Fischer rats unde…