Structural changes in the blood vessels and parenchyma of the lungs in experimental hypercholesterolemia and atherosclerosis

Klimenko, E. D.; Pozdnyakov, O. M.

doi:10.1007/bf00839329

Cited by 2 publications

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“…However, our study with Apoe knockout mice, which have disordered lipid metabolism including hypercholesterolemia (38), earlier work by others indicating hypercholesterolemia in rabbits results in senile emphysema (14), and the marked increase of 15-lipoxygenase in lung and heart in mice fed a high cholesterol diet (1), suggest the influence of diet, genetics, or both on lipid metabolism, is the more upstream mediator of the concurrence of COPD and cardiovascular disease than is inflammation and oxidative stress (17,33).…”

Section: Discussionmentioning

confidence: 50%

“…However, in animals, a diet high in cholesterol produces atheromatous changes in the pulmonary vasculature (5,6,8,13,30). Providing rabbits with a diet high in cholesterol results in "senile emphysema" and has led to the suggestion that disordered lipid metabolism results in abnormal pulmonary alveoli (14). This latter notion is supported by our present findings, and, on a more mechanistic level, by the demonstration that a high cholesterol diet in rabbits induces in the lung a several hundred-fold elevation of 15-lipoxygenase activity (1); the latter has a pro-as well as an anti-inflammatory effect, and may have a proathrogenic effect (for review, see Ref.…”

Section: Discussionmentioning

confidence: 99%

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Apoe^tm1Unc mice have impaired alveologenesis, low lung function, and rapid loss of lung function

Massaro¹,

Massaro²

2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Massaro D, Massaro GD. Apoe tm1Unc mice have impaired alveologenesis, low lung function, and rapid loss of lung function. Am J Physiol Lung Cell Mol Physiol 294: L991-L997, 2008. First published March 14, 2008 doi:10.1152/ajplung.00013.2008.-Diminished lung function, indicated by a low forced expiratory volume in one second (FEV1), and short physical stature, predict early mortality from all causes, including cardiovascular, among smokers and never smokers. The basis for these associations is unclear, and, it is not known if there is a pulmonary morphological component to the relationship between low FEV 1 and early death in a general population. Some apolipoprotein E genotypes also predict atherosclerosis and early mortality. These considerations led us to examine the Apoe tm1Unc (Apoe) mouse, in which the apolipoprotein E gene is deleted, and that develops dyslipidemia, atherosclerosis at an early age, and has a shorter life span than the founder wild-type (wt) strain. We asked if Apoe mice have a morphological or functional pulmonary phenotype. We measured the size, number, and surface area of pulmonary gas-exchange units (alveoli) and mechanical properties of the lung. Compared with wt mice, Apoe mice had: 1) diminished developmental alveologenesis, 2) increased airway resistance in early adulthood, 3) high lung volume and high dynamic and static compliance in later adulthood, 4) more rapid loss of lung recoil with age, and 5) were less long than wt mice. These findings in mice indicate the association of a low FEV1 with early death in humans may have developmental, and accelerated ageing, related pulmonary components, and that dietary, genetic, or dietary and genetic influences, on lipid metabolism may be an upstream cause of inflammation and oxidative stress, currently considered to be major risk factors for COPD.FEV1; predict early death; atherosclerosis; short stature; diet; genetics; cholesterol EPIDEMIOLOGICAL STUDIES INDICATE that in a general population of never smokers or smokers, a low forced expiratory volume in one second (FEV 1 ), compared with its expected value, is a predictor of early mortality from all causes, including cardiovascular (3, 33). Why FEV 1 has this predictive capacity in a general population, especially among never smokers, is unclear. A putative factor linking a low for expected FEV 1 to cardiovascular disease is evidence of the presence of chronic systemic inflammation, based on finding elevated concentrations of markers of systemic inflammation, in individuals with a low FEV 1 (31), and in those with cardiovascular disease (34). Oxidative stress is also considered a risk factor for cardiovascular disease (34), for a low FEV 1 in a general population (26), and for chronic obstructive pulmonary disease (COPD), which is a cause of a low FEV 1 (27). However, in COPD, there are morphological abnormalities associated with, and indicative of, a low FEV 1 (10). In contrast, it is not known if in a general population without COPD, or without other identified pulmonary diseases, a pu...

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Apoe^tm1Unc mice have impaired alveologenesis, low lung function, and rapid loss of lung function

Massaro¹,

Massaro²

2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Group 3 rabbits were intramuscularly injected with verapamil (phynoptin, Orion) in a dose of 0.5 mg/kg for 10 days during the 2nd month of the diet. We previously observed marked accumulation of LDL, pronounced changes in HPNS, peripheral subdivision of SAS (adrenergic innervation of microvessels), and microcirculatory vascular bed, and initial lipidosis of the aortal intima after one month of ATD [3,5]. Plasma level of total HDL and LDL fractions were determined.…”

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confidence: 99%

Correction of disturbances in neuroregulatory systems at early stages of atherogenesis with verapamil

et al. 2000

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The effect of verapamil on morphofunctional state of the hypothalamo-pituitary neurosecretory system, adrenergic innervation of microvessels, and microcirculation in the early stages of atherogenesis was studied. Correction of functional aberrations of the neuroregulatory systems and microcirculatory disturbances with verapamil was accompanied by restoration of lipid homeostasis and less pronounced atherosclerotic alterations in major arteries. Key Words: verapamil; hypothalamo-pituitary neurosecretory system; adrenergic innervation of microvessels; atherosclerosisThe hypothalamo-pituitary neurosecretory system (HPNS) and peripheral subdivision of the sympathoadrenal system (SAS), which produce bioactive substances with vasoactive and lipid mobilizing effect (vasopressin, norepinephrine), play an important role in the mechanisms of atherogenesis. There is a correlation between functional state of these systems, microcirculatory disturbances, and the degree of atherosclerotic process in major arteries during hyperlipemia [2,5,8].In view of the priming role of microcirculatory disturbances in the development of polyorgan pathology during hyperlipidemia [4], the search for means of correction of functional disturbances in HPNS and SAS is actual. It was established that some calcium channel blockers affect lipid metabolism and modulate activity of the antioxidant system and SAS [7,10,11]. Calcium blocker verapamil is an active neuroprotector, which protects, in particularly, the neurosecretory pituitary cells [6].Our aim was to study the effect of verapamil on morphofunctional state of the regulatory systems at the early stages of atherogenesis. MATERIALS AND METHODSExperiments were performed on 30 male Chinchilla rabbits weighing 2.5-3.0 kg. Group 1 rabbits (intact controls) were maintained on a standard diet. Group 2 rabbits were given 0.3 g/kg cholesterol during 2 months, which modeled atherogenic diet (ATD) according to N. N. Anichkov. Group 3 rabbits were intramuscularly injected with verapamil (phynoptin, Orion) in a dose of 0.5 mg/kg for 10 days during the 2nd month of the diet. We previously observed marked accumulation of LDL, pronounced changes in HPNS, peripheral subdivision of SAS (adrenergic innervation of microvessels), and microcirculatory vascular bed, and initial lipidosis of the aortal intima after one month of ATD [3,5]. Plasma level of total HDL and LDL fractions were determined. The degree of atherosclerotic process was assessed by the index of atherosclerotic damage (lAD) to the aorta [13]. The hypothalamic supraoptic (SO) nuclei and neurohypophysis were studied on serial brain slices by the methods of Gomori--Maiorova, Nissl, and Milenkov. The functional state of HPNS was assessed as described elsewhere [9] by the content of Gomori-positive substance in neurosecretory cells, hypothalamo-pituitary tract, and posterior pituitary. The percentage of "bright" and

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Structural changes in the blood vessels and parenchyma of the lungs in experimental hypercholesterolemia and atherosclerosis

Cited by 2 publications

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Apoe^tm1Unc mice have impaired alveologenesis, low lung function, and rapid loss of lung function

Apoe^tm1Unc mice have impaired alveologenesis, low lung function, and rapid loss of lung function

Correction of disturbances in neuroregulatory systems at early stages of atherogenesis with verapamil

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Structural changes in the blood vessels and parenchyma of the lungs in experimental hypercholesterolemia and atherosclerosis

Cited by 2 publications

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Apoetm1Unc mice have impaired alveologenesis, low lung function, and rapid loss of lung function

Apoetm1Unc mice have impaired alveologenesis, low lung function, and rapid loss of lung function

Correction of disturbances in neuroregulatory systems at early stages of atherogenesis with verapamil

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Apoe^tm1Unc mice have impaired alveologenesis, low lung function, and rapid loss of lung function

Apoe^tm1Unc mice have impaired alveologenesis, low lung function, and rapid loss of lung function