Molecular and cellular basis of pulmonary vascular remodeling in pulmonary hypertension☆
Section snippets
Normal morphology of the pulmonary vasculature
One of the main functions of the normal pulmonary circulation is respiratory gas exchange. To fulfil this purpose efficiently, the pulmonary circulation is a low-pressure, high-flow system with a great capacity for recruitment of normally unperfused vessels. The walls of the pulmonary arteries are therefore relatively thin, in keeping with their low transmural pressure. The anatomy of pulmonary arteries alters in a systematic way from the central “conduit” arteries to the peripheral
The role of growth factors
Many factors must act in concert to orchestrate the process of pulmonary vascular remodeling. However, recent advances in our understanding of the pathogenesis of primary pulmonary hypertension at the genetic and molecular level have suggested that alterations in certain key pathways may play a central role in initiating disease or contribute to disease progression.
Cell cycle
One of the major targets for any proliferative or anti-proliferative stimuli is the cell cycle, a strategy used by the cell to duplicate its contents and hence divide. Various regulators control each of the 5 phases of the cell cycle. Complexes of cyclins and cyclin-dependent kinases (cdk) are positive regulators, and their successive activation allows progression through each phase of the cycle resulting in cell replication. However, progression of the cell cycle can be inhibited by
Mechanisms regulating pulmonary vascular apoptosis
Apoptosis, or programmed cell death, is an important physiologic process regulating the homeostasis of cells. Thus, either excessive or limited apoptosis can lead to the development of a variety of diseases including pulmonary hypertension. The mechanisms of programmed cell death are complex, occurring through multiple independent pathways, and vary depending on cell type (reviewed in references 287 to 289). However, there are a number of common factors/mediators involved, and alterations in
Summary
Recent years have seen great progress in our understanding of the molecular and cellular mechanisms, which contribute to the maintenance of the normal pulmonary circulation and to the pathologic changes associated with pulmonary hypertension. These advances have come both from the identification of specific genes and from careful hypothesis-driven examination of regulatory pathways. On the one hand, this research has highlighted the enormous complexity of the biological systems that regulate
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Therapeutic potential and protective role of GRK6 overexpression in pulmonary arterial hypertension
2023, Vascular PharmacologySulforaphane alleviated vascular remodeling in hypoxic pulmonary hypertension via inhibiting inflammation and oxidative stress
2023, Journal of Nutritional BiochemistryCitation Excerpt :The pathogenesis of HPH is mainly characterized by inflammation, oxidative stress, abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs), and dysfunction of endothelial cells (ECs) [4–6]. Pulmonary vascular remodeling is a complicated pathologic process that involves intima, media, and adventitia thickening of the distal pulmonary arteries [7]. The cellular basis includes cell hyperplasia, migration, as well as generation and redistribution of extracellular matrix, which finally leads to the narrowing and obliteration of the vessel lumen and formation of plexiform lesions [7,8].
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2021, Journal of Drug Delivery Science and TechnologyCitation Excerpt :Moreover, in extreme cases, this excessive vascular smooth muscle cell proliferation can develop vascular plexiform lesions and their calcification. This is more pronounced in our study in the hypoxia-induced PH rat model [45]. In the hypoxia group (Fig. 6), the pulmonary artery showed the thickening of the lumen diameter contributing to pulmonary arterial remodeling involving proliferation and masculinization of arterial smooth muscle cells.
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Address reprint requests to Nicholas W. Morrell, MD FRCP, Respiratory Medicine Unit, Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.