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Fibulin-5 null mice with decreased arterial compliance maintain normal systolic left ventricular function, but not diastolic function during maturation.

ABSTRACT: Abstract The large arteries serve as compliant vessels that store energy during systole and return it during diastole. This function is made possible by the elastic fibers in the arterial wall that are assembled during late embryonic and early postnatal development from various proteins, including fibulin-5. Mice and humans with insufficient amounts of fibulin-5 have reduced arterial compliance as adults. Reduced compliance of the large arteries is correlated with hypertension, reduced cardiac function, and an increased risk of death from cardiac and cardiovascular disease. The goal of this study was to quantify arterial compliance, blood pressure, and left ventricular (LV) function from early postnatal development to young adulthood in fibulin-5 null (Fbln5-/-) mice to determine the effects of reduced arterial compliance during this critical period of elastic fiber assembly. We find that ascending aorta compliance is reduced as early as postnatal day (P) 7 and carotid artery compliance is reduced by P21 in Fbln5-/- mice. We did not find significant increases in systolic blood pressure by P60, but pulse pressures are increased by P21 in Fbln5-/- mice. LV systolic function, as measured by ejection fraction and fractional shortening, is unaffected in Fbln5-/- mice. However, LV diastolic function, as measured by tissue Doppler imaging, is compromised at all ages in Fbln5-/- mice. We propose that Fbln5-/- mice represent a suitable model for further studies to determine mechanistic relationships between arterial compliance and LV diastolic function.

SUBMITTER: Le VP

PROVIDER: S-EPMC4002237 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Fibulin-5 null mice with decreased arterial compliance maintain normal systolic left ventricular function, but not diastolic function during maturation.

Le Victoria P VP Stoka Kellie V KV Yanagisawa Hiromi H Wagenseil Jessica E JE

Physiological reports 20140320 3

Abstract The large arteries serve as compliant vessels that store energy during systole and return it during diastole. This function is made possible by the elastic fibers in the arterial wall that are assembled during late embryonic and early postnatal development from various proteins, including fibulin-5. Mice and humans with insufficient amounts of fibulin-5 have reduced arterial compliance as adults. Reduced compliance of the large arteries is correlated with hypertension, reduced cardiac f ...[more]

PMID: 24760511

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Project description:Background and Objectives: No data are available on whether the heritability of left ventricle (LV) systolic and diastolic parameters are independent of each other. Therefore, our aim was to assess the magnitude of common and independent genetic and environmental factors defining LV systolic and diastolic function. Materials and Methods: We analyzed 184 asymptomatic twins (65% female, mean age: 56 ± 9 years). Transthoracic echocardiography was performed to measure LV systolic (global longitudinal and circumferential strain; basal and apical rotation) and diastolic (early diastolic velocity of mitral inflow and lateral mitral annulus tissue; deceleration time and early diastolic strain rate) parameters using conventional and speckle-tracking echocardiography. Genetic structural equation models were evaluated to quantify the proportion of common and specific genetic (Ac, As) and environmental factors (Ec, Es) contributing to the phenotypes. Results: LV systolic parameters had no common genetic or environmental heritability (Ac range: 0-0%; Ec range: 0-0%; As range: 57-77%; Es range: 24-43%). Diastolic LV parameters were mainly determined by common genetic and environmental effects (Ac range: 9-40%; Ec range: 11-49%; As range: 0-29%; Es range: 0-51%). Systolic parameters had no common genetic or environmental factors (Ac = 0%; Ec = 0%) with diastolic metrics. Conclusions: Systolic LV parameters have a strong genetic predisposition to any impact. They share no common genetic or environmental factors with each other or with diastolic parameters, indicating that they may deteriorate specifically to given effects. However, diastolic functional parameters are mainly affected by common environmental influences, suggesting that pathological conditions may deteriorate them equally. Estimation of the genetic and environmental influence and interdependence on systolic and diastolic LV function may help the understanding of the pathomechanism of different heart failure classification types.

Project description:Background: Sports athletes, namely high-intensity practitioners, suffer from vascular remodeling overtime. The purpose of this study was to analyze the systolic and diastolic velocities' variation between non-athletes and futsal athletes by means of arterial lower limb doppler ultrasound. Additionally, we intended to verify if the velocity variations occur primarily at the systolic or the diastolic level and in which arteries. Methods: Seventy-six young males (mean ± SD: 24.9 ± 2.8 years old) volunteered to participate in this cross-sectional study and were divided into two groups: a futsal athletes group (n = 38; 24 ± 2.78 years) in the central region of Portugal playing on the 2nd national league with the same level of practice (16 ± 2.4 years of practice) and a non-athletes group (n = 38: 26 ± 1.8 years) who did not practice sports regularly and were not federated in any sport. All the subjects agreed to participate in the study with the aim of assessing the arterial lower limb through doppler ultrasound (Philips HD7 echograph with linear transducer 7-12 MHz). Results: Differences between groups (p ? 0.05) in the systolic velocity of the left deep femoral artery (p = 0.022; d = 0.546, small) and in the right superficial femoral artery (p = 0.028; d = -0.515, small) were found. We also found differences in the diastolic velocity: in the left common femoral artery (p = 0.002; d = -0.748, moderate), in the right deep femoral artery (p = 0.028; d = -0.521, small), in the right superficial femoral artery (p = 0.026; d = -0.522, small), in the right popliteal artery (p = 0.002; d = -0.763, moderate), and in the left popliteal artery (p = 0.007; d = -0.655, moderate). Moreover, the athletes' group presented the highest mean values, with the exception of the systolic velocity of the left deep femoral artery. In intragroup analysis of variance referring to systolic and diastolic velocities in arterial levels in the right and left arteries, differences were found in all analyses (p ? 0.05). Conclusions: We conclude that futsal athletes of our sample go through a process of changes such as increased blood flow velocity in systolic and diastolic cardiac phase in all studied lower limb arteries, showing that the remodeling occurs regardless of vessel radius. Our results reinforce the existence of vascular remodeling that may vary with the sport and its intensity.

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Fibulin-5 null mice with decreased arterial compliance maintain normal systolic left ventricular function, but not diastolic function during maturation.

Publications

Fibulin-5 null mice with decreased arterial compliance maintain normal systolic left ventricular function, but not diastolic function during maturation.

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