Pulmonary atherosclerosis associated with an atrial septal defect in old age: Case report of an elderly autopsied patient

Nascimento, Douglas Montielle Silva; Nunes, Lucas Martins de Exel; Oliveira, Flávia Aparecida de; Vêncio, Eneida Franco; Teixeira, Vicente de Paula Antunes; Reis, Marlene Antônia dos

doi:10.1016/j.prp.2008.07.008

Cited by 8 publications

(5 citation statements)

References 13 publications

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“…The causal relationship between PA atherosclerosis and PH is not clear. PA atherosclerosis has been observed in patients with diseases that cause PH, such as atrial septal defect and shunt and chronic obstructive pulmonary disease (Russo et al, 1999;Nascimento et al, 2009), and was associated with hypertensive pulmonary vascular disease (Moore et al, 1982). As a matter of fact, OSA patients have elevated PA pressure (Minai et al, 2009) and a higher incidence of acute pulmonary embolism (Alonso-Fernandez et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Influence of Intermittent Hypoxia/Hypercapnia on Atherosclerosis, Gut Microbiome, and Metabolome

et al. 2021

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Obstructive sleep apnea (OSA), a common sleep disorder characterized by intermittent hypoxia and hypercapnia (IHC), increases atherosclerosis risk. However, the contribution of intermittent hypoxia (IH) or intermittent hypercapnia (IC) in promoting atherosclerosis remains unclear. Since gut microbiota and metabolites have been implicated in atherosclerosis, we examined whether IH or IC alters the microbiome and metabolome to induce a pro-atherosclerotic state. Apolipoprotein E deficient mice (ApoE−/−), treated with IH or IC on a high-fat diet (HFD) for 10 weeks, were compared to Air controls. Atherosclerotic lesions were examined, gut microbiome was profiled using 16S rRNA gene amplicon sequencing and metabolome was assessed by untargeted mass spectrometry. In the aorta, IC-induced atherosclerosis was significantly greater than IH and Air controls (aorta, IC 11.1 ± 0.7% vs. IH 7.6 ± 0.4%, p < 0.05 vs. Air 8.1 ± 0.8%, p < 0.05). In the pulmonary artery (PA), however, IH, IC, and Air were significantly different from each other in atherosclerotic formation with the largest lesion observed under IH (PA, IH 40.9 ± 2.0% vs. IC 20.1 ± 2.6% vs. Air 12.2 ± 1.5%, p < 0.05). The most differentially abundant microbial families (p < 0.001) were Peptostreptococcaceae, Ruminococcaceae, and Erysipelotrichaceae. The most differentially abundant metabolites (p < 0.001) were tauro-β-muricholic acid, ursodeoxycholic acid, and lysophosphoethanolamine (18:0). We conclude that IH and IC (a) modulate atherosclerosis progression differently in distinct vascular beds with IC, unlike IH, facilitating atherosclerosis in both aorta and PA and (b) promote an atherosclerotic luminal gut environment that is more evident in IH than IC. We speculate that the resulting changes in the gut metabolome and microbiome interact differently with distinct vascular beds.

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Section: Discussionmentioning

confidence: 99%

Influence of Intermittent Hypoxia/Hypercapnia on Atherosclerosis, Gut Microbiome, and Metabolome

et al. 2021

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“…Atherosclerosis typically develops only in vascular segments, which are exposed to high intraluminal pressure, whereas the pulmonary circulation is characterized by low blood pressure. Recent reports suggest that severe atherosclerosis can develop in pulmonary arteries of old patients in the presence of pulmonary hypertension (e.g., due to an atrial septal defect) (47). The findings that age-related endothelial dysfunction is also present in the low-pressure region of the systemic microcirculation argue against the hypothesis that age-related endothelial oxidative stress is due to the increased systolic blood pressure (39, 52).…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress and endothelial dysfunction in pulmonary arteries of aged rats

Podlutsky

Ballabh

Csiszár

2010

American Journal of Physiology-Heart and Circulatory Physiology

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Aging in the systemic circulation is associated with generalized endothelial dysfunction and increased oxidative stress, which are thought to contribute to the increased morbidity and mortality of cardiovascular diseases in the elderly. Previous studies have shown that pulmonary artery pressure and vascular resistance increase with normal aging in humans, yet age-related functional and phenotypic changes in the pulmonary arteries have not been characterized. To determine whether in the pulmonary circulation aging elicits endothelial dysfunction and oxidative stress, isolated pulmonary arteries of young (3 mo old) and aged (28 mo old) F344 rats were compared. We found that aging in rat pulmonary arteries is associated with impaired acetylcholine-induced relaxation and vascular oxidative stress [assessed by dihydroethidine and 5 (and 6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate-acetyl ester fluorescence assays]. Endothelial dysfunction in the aged pulmonary vessels is reversed by the inhibition of NAD(P)H oxidase. The expressions of gp91(phox) (both mRNA and protein), NAD(P)H oxidase isoform type 1 (Nox-1; mRNA), and Nox-4 (mRNA) tend to increase in aged vessels; however, only changes in Nox-4 reached statistical significance. In pulmonary arteries of aged rats, the protein expression of endothelial nitric oxide synthase, Cu,Zn-SOD, Mn-SOD, and glutathione peroxidase is unaltered, whereas the expression of catalase is significantly decreased. Our results suggest that aging is associated with oxidative stress and endothelial dysfunction in the pulmonary arteries, which may contribute to the age-related functional alterations in the pulmonary circulation.

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“…Therefore, we speculate that PA atherosclerosis could be present in OSA patients, and, to our knowledge we are not certain that this has been adequately investigated in the past. There has been very little information about PA atherosclerosis in the mouse (20,29), although it has been reported more frequently in bigger animals such as rabbits (14,17,33,41,42,46). We suspect that it is possible that PA atherosclerosis in the mouse might have been missed in previous investigations.…”

Section: Discussionmentioning

confidence: 94%

Intermittent hypoxia and hypercapnia induces inhibitor of nuclear factor-κB kinase subunit β-dependent atherosclerosis in pulmonary arteries

Imamura

Xue

Poulsen

et al. 2019

American Journal of Physiology-Regulatory, Integrative and Comp

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Clinical studies have shown that obstructive sleep apnea (OSA) increases atherosclerosis risk. The inflammation, especially mediated by the macrophages via nuclear factor-κB (NF-κB), has been speculated to contribute to atherogenicity in OSA patients. Inhibitor of NF-κB kinase-β (IKKβ) is an essential element of the NF-κB pathway and is linked to atherosclerosis. We previously reported that atherosclerosis was accelerated in pulmonary artery (PA) but not in aorta when low-density lipoprotein receptor knockout ( Ldlr−/−) mice were exposed to intermittent hypoxia/hypercapnia (IHH), a surrogate for recurrent upper-airway obstruction. Therefore, we hypothesized that IKKβ-dependent NF-κB activation in monocytes and macrophages plays a role in IHH-induced PA atherosclerosis. To test this hypothesis, myeloid restricted IKKβ deletion ( IkkβΔMye) or control ( IkkβF/F) mice were crossed with Ldlr−/− mice to generate double-knockout mice. Then, the mice were exposed to IHH or room air (Air) on high-fat diet for 8 or 16 wk. Lesions of PA and aorta were examined in IkkβΔMye; Ldlr−/− and IkkβF/F; Ldlr−/− male mice under IHH vs. Air. The results revealed that IKKβ deletion abolished IHH-induced PA atherosclerosis after 8-wk exposure but not after 16-wk exposure (8 wk: IkkβF/F; Ldlr−/−, IHH 13.5 ± 1.4 vs. Air 5.7 ± 0.7%, P < 0.01; IkkβΔMye; Ldlr−/−, IHH 7.4 ± 1.9% vs. Air 4.6 ± 1.3%, P = 0.24). Both IKKβ deletion and IHH had no effects on atherosclerosis in the aorta. Our findings demonstrate that IKKβ-dependent NF-κB activity in myeloid-lineage cells plays a critical role in IHH-induced PA atherosclerosis at the early stage.

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Pulmonary atherosclerosis associated with an atrial septal defect in old age: Case report of an elderly autopsied patient

Cited by 8 publications

References 13 publications

Influence of Intermittent Hypoxia/Hypercapnia on Atherosclerosis, Gut Microbiome, and Metabolome

Influence of Intermittent Hypoxia/Hypercapnia on Atherosclerosis, Gut Microbiome, and Metabolome

Oxidative stress and endothelial dysfunction in pulmonary arteries of aged rats

Intermittent hypoxia and hypercapnia induces inhibitor of nuclear factor-κB kinase subunit β-dependent atherosclerosis in pulmonary arteries

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