Cuff-induced vascular intima thickening is influenced by titration of the Ace gene in mice

Lacchini, Sílvia; Heimann, Andrea S.; Evangelista, Fabiana S.; Cardoso, Leandro Lunardini; Silva, Gustavo J. J.

doi:10.1152/physiolgenomics.90288.2008

Cited by 10 publications

(19 citation statements)

References 36 publications

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“…Similarly, in the present study, when the increase in BP produced by renovascular hypertension was permanent, the LV hypertrophy observed for the same increase in pressure was enhanced in mice with three copies of the Ace gene compared with those with only two. We have also demonstrated that the Ace genotype confers different vascular remodelling in mice 24 . Cuff‐induced vascular intima thickening in both femoral and carotid arteries was higher in mice with three and four copies of the gene compared with those with only one or two copies 24 .…”

Section: Discussionmentioning

confidence: 60%

Ace gene dosage influences the development of renovascular hypertension

Ceroni

Moreira

Mostarda

et al. 2010

Clin Exp Pharma Physio

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1. Clinical and experimental evidence highlights the importance of the renin-angiotensin system in renovascular hypertension. Furthermore, genetic factors affecting angiotensin-converting enzyme (ACE) could influence the development of renovascular hypertension. 2. To test the effect of small gene perturbations on the development of renovascular hypertension, mice harbouring two or three copies of the Ace gene were submitted to 4 weeks of two-kidney, one-clip (2K1C) hypertension. Blood pressure (BP), cardiac hypertrophy, baroreflex sensitivity and blood pressure and heart rate variability were assessed and compared between the different groups. 3. The increase in BP induced by 2K1C was higher in mice with three copies of the Ace gene compared with mice with only two copies (46 vs 23 mmHg, respectively). Moreover, there was a 3.8-fold increase in the slope of the left ventricle mass/BP relationship in mice with three copies of the Ace gene. Micewith three copies of the Ace gene exhibited greater increases in cardiac and serum ACE activity than mice with only two copies of the gene. Both baroreflex bradycardia and tachycardia were significantly depressed in mice with three copies of the Ace gene after induction of 2K1C hypertension. The variance in basal systolic BP was greater in mice with three copies of the Ace gene after 2K1C hypertension compared with those with only two copies of the gene (106 vs 54%, respectively). In addition, the low-frequency component of the pulse interval was higher mice with three copies of the Ace gene after 2K1C hypertension compared with those with only two (168 vs 86%, respectively). Finally, in mice with three copies of the Ace gene, renovascular hypertension induced a 6.1-fold increase in the sympathovagal balance compared with a 3.2-fold increase in mice with only two copies of the gene. 4. Collectively, these data provide direct evidence that small genetic disturbances in ACE levels per se have an influence on haemodynamic, cardiac mass and autonomic nervous system responses in mice under pathological perturbation.

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Section: Discussionmentioning

confidence: 60%

Ace gene dosage influences the development of renovascular hypertension

Ceroni

Moreira

Mostarda

et al. 2010

Clin Exp Pharma Physio

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“…This RAS activation may not be essential during the adaptation to hypertension, but it must be essential in a late process, either related to heart failure32 or to vascular injury 33…”

Section: Discussionmentioning

confidence: 99%

Hemodynamic, Morphometric and Autonomic Patterns in Hypertensive Rats - Renin-Angiotensin System Modulation

Zamo¹,

Lacchini²,

Mostarda³

et al. 2010

Clinics

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BACKGROUND:Spontaneously hypertensive rats develop left ventricular hypertrophy, increased blood pressure and blood pressure variability, which are important determinants of heart damage, like the activation of renin-angiotensin system.AIMS:To investigate the effects of the time-course of hypertension over 1) hemodynamic and autonomic patterns (blood pressure; blood pressure variability; heart rate); 2) left ventricular hypertrophy; and 3) local and systemic Renin-angiotensin system of the spontaneously hypertensive rats.METHODS:Male spontaneously hypertensive rats were randomized into two groups: young (n=13) and adult (n=12). Hemodynamic signals (blood pressure, heart rate), blood pressure variability (BPV) and spectral analysis of the autonomic components of blood pressure were analyzed. LEFT ventricular hypertrophy was measured by the ratio of LV mass to body weight (mg/g), by myocyte diameter (μm) and by relative fibrosis area (RFA, %). ACE and ACE2 activities were measured by fluorometry (UF/min), and plasma renin activity (PRA) was assessed by a radioimmunoassay (ng/mL/h). Cardiac gene expressions of Agt, Ace and Ace2 were quantified by RT-PCR (AU).RESULTS:The time-course of hypertension in spontaneously hypertensive rats increased BPV and reduced the alpha index in adult spontaneously hypertensive rats. Adult rats showed increases in left ventricular hypertrophy and in RFA. Compared to young spontaneously hypertensive rats, adult spontaneously hypertensive rats had lower cardiac ACE and ACE2 activities, and high levels of PRA. No change was observed in gene expression of Renin-angiotensin system components.CONCLUSIONS:The observed autonomic dysfunction and modulation of Renin-angiotensin system activity are contributing factors to end-organ damage in hypertension and could be interacting. Our findings suggest that the management of hypertensive disease must start before blood pressure reaches the highest stable levels and the consequent established end-organ damage is reached.

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“…ACE activity in aortae extracts was determined using Abz-FRK(Dnp)P-OH derivatives as substrates by continuously measuring the fluorescence according to our previous publications [21, 22]. Tissue samples were quickly harvested, homogenized in Tris-HCl buffer, pH 7.0, containing 50 mM NaCl, and centrifuged at 1,000 g for 10 min.…”

Section: Methodsmentioning

confidence: 99%

“…Fluorescence increments along the time were read at 420 nm emission: 320 nm excitation. Tissue ACE activity was expressed as fluorescence units (AFU)·min −1 ·mg −1 of protein [21, 22]. The protein content was determined by the Bradford method by using bovine serum albumin as the standard (Bio-Rad protein assay).…”

Section: Methodsmentioning

confidence: 99%

Effect of High-Fat Diet upon Inflammatory Markers and Aortic Stiffening in Mice

Santana

Oliveira

Bianconi

et al. 2014

BioMed Research International

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Changes in lifestyle such as increase in high-fat food consumption are an important cause for vascular diseases. The present study aimed to investigate the involvement of ACE and TGF-β in the aorta stiffness induced by high-fat diet. C57BL/6 male mice were divided in two groups according to their diet for 8 weeks: standard diet (ST) and high-fat diet (HF). At the end of the protocol, body weight gain, adipose tissue content, serum lipids and glucose levels, and aorta morphometric and biochemical measurements were performed. Analysis of collagen fibers by picrosirius staining of aorta slices showed that HF diet promoted increase of thin (55%) and thick (100%) collagen fibers deposition and concomitant disorganization of these fibers orientations in the aorta vascular wall (50%). To unravel the mechanism involved, myeloperoxidase (MPO) and angiotensin I converting enzyme (ACE) were evaluated by protein expression and enzyme activity. HF diet increased MPO (90%) and ACE (28%) activities, as well as protein expression of ACE. TGF-β was also increased in aorta tissue of HF diet mice after 8 weeks. Altogether, we have observed that the HF diet-induced aortic stiffening may be associated with increased oxidative stress damage and activation of the RAS in vascular tissue.

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Cuff-induced vascular intima thickening is influenced by titration of the Ace gene in mice

Abstract: Lacchini S, Heimann AS, Evangelista FS, Cardoso L, Silva GJ, Krieger JE. Cuff-induced vascular intima thickening is influenced by titration of the Ace gene in mice.

Cited by 10 publications

References 36 publications

Ace gene dosage influences the development of renovascular hypertension

Ace gene dosage influences the development of renovascular hypertension

Hemodynamic, Morphometric and Autonomic Patterns in Hypertensive Rats - Renin-Angiotensin System Modulation

Effect of High-Fat Diet upon Inflammatory Markers and Aortic Stiffening in Mice

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