Primary pulmonary hypertension a case report including electronmicroscopic study

Meyrick, Barbara; Clarke, S W; Symons, Cecil; Woodgate, D.J.; Reid, Lynne

doi:10.1016/0007-0971(74)90003-5

Cited by 29 publications

(9 citation statements)

References 8 publications

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“…It is the latter change that is the focus of this debate. While many groups have reported loss of vessels during exposure of rodents to chronic hypoxia (10,11,15,16,18,25,26,29), several other groups could find no such loss (3,5,6,14,17,19) and more recently some have provided evidence of new vessel formation in the pulmonary vasculature in response to sustained hypoxia (1,12,13,22).…”

Section: However This Does Not Negate the Loss Of Vessels Only Thatmentioning

confidence: 99%

“…Experimental stimuli in addition to chronic hypoxia that induce loss of vessels in association with pulmonary hypertension have included injection of the toxin monocrotaline (23), monocrotaline and pneumonectomy (17), exposure to chronic hyperoxia (11,22), and creation of aortopulmonary shunts (19). In the clinical setting, conditions associated with pulmonary hypertension and loss of arteries include congenital heart defects (18), lung developmental abnormalities (2), and idiopathic pulmonary hypertension (16). Improved resolution of current imaging techniques might, in the future, detect loss of precapillary arteries in association with pulmonary hypertension in the clinical setting.…”

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confidence: 99%

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Point:Counterpoint: Chronic hypoxia-induced pulmonary hypertension does/does not lead to loss of pulmonary vasculature

Rabinovitch¹,

Chesler²,

Molthen³

2007

Journal of Applied Physiology

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Section: However This Does Not Negate the Loss Of Vessels Only Thatmentioning

confidence: 99%

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confidence: 99%

Point:Counterpoint: Chronic hypoxia-induced pulmonary hypertension does/does not lead to loss of pulmonary vasculature

Rabinovitch¹,

Chesler²,

Molthen³

2007

Journal of Applied Physiology

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“…They may represent a specialized subpopulation of SMCs; they may originate as stem cells (8) or fibrocytes (9) or transform from ECs (10,11). The loss of distal PAs could be caused by alterations in ECs and/or pericytes resulting in apoptosis (12).…”

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confidence: 99%

Molecular pathogenesis of pulmonary arterial hypertension

Rabinovitch¹

2012

J. Clin. Invest.

691

649

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Pathological features of PAHPulmonary arterial hypertension (PAH) is diagnosed by an elevation in mean pulmonary arterial (PA) pressure above 25 mmHg at rest or 30 mmHg with exercise. Patients usually present with much higher levels of PA pressure, but only vague and insidious symptoms of increasing fatigue and dyspnea; some patients are diagnosed only after syncopal episodes, which can reflect suprasystemic levels of PA pressure and low cardiac output. The causes of PAH were reclassified according to a consensus at the Fourth World While this review focuses on pulmonary hypertension category 1 (i.e., PAH), pathophysiologic insights can also be gained from understanding other causes of pulmonary hypertension. Hence, experimental studies in hypoxic animals are also discussed.In neonates and in infants, PAH likely results from failure of the neonatal pulmonary vasculature to dilate at birth, and pathological changes in the blood vessels are evident in the first few days of life. Most prominent is abnormal muscularization of distal PAs at the alveolar duct and wall levels and a striking reduction in their number. In older infants and adults, there is also progressive intimal hyperplasia leading to occlusive changes in the PAs and plexiform lesions (Figure 1 and see below).PA EC alterations in the clinical (2) and experimental (3) setting precede muscularization of distal PAs. In PA ECs from patients with idiopathic PAH (IPAH), an increase in Tie2 receptor expression in ECs releases serotonin, mediating SMC proliferation (4). Dysfunctional ECs can either release factors that stimulate SMC proliferation, such as FGF-2 (5), or fail to produce agents that normally suppress proliferation of SMCs in response to growth factors, such as apelin (encoded by Apln) (6).Muscularization of distal, normally nonmuscular, PAs at the alveolar duct and wall level is associated with differentiation of pericytes into SMCs that subsequently proliferate. The progressive thickening of the wall of more proximal intraacinar and preacinar muscular arteries and the obliteration associated with neointimal formation are attributed to increased proliferation and migration of cells considered to be SMCs because they are α-SMA positive (7). The origin of these cells is unclear, and the mechanism of their dysregulation is the subject of intense study. They may represent a specialized subpopulation of SMCs; they may originate as stem cells (8) or fibrocytes (9) or transform from ECs (10, 11). The loss of distal PAs could be caused by alterations in ECs and/or pericytes resulting in apoptosis (12).Later in disease, there is dysregulated EC proliferation, producing aberrant channels in the otherwise obliterated lumen of the vessel and in the adventitia (i.e., the plexiform lesion). These channels may reflect clonal expansion of apoptosis-resistant ECs (13), or they may be derived from circulating endothelial progenitor cells (EPCs) that accumulate at sites of endothelial denudation or injury and expand locally (14). PA ECs from patients with IPAH prod...

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“…These cells may represent a specialized subpopulation of SMCs, they may have originated as stem cells or fibrocytes (5), or they may even have arisen from ECs (6). The loss of distal vessels could be due to alterations in ECs and/or pericytes resulting in apoptosis (7). Endothelial alterations have been noted in pulmonary arteries of PAH patients (8) and in the experimental setting (9) to precede the development of muscularization of PAs.…”

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confidence: 99%