Increased hyaluronic acid content in idiopathic pulmonary arterial hypertension

Papakonstantinou, Eleni; Kouri, Fotini M.; Karakiulakis, George; Klagas, Ioannis; Eickelberg, Oliver

doi:10.1183/09031936.00159507

Cited by 51 publications

(64 citation statements)

References 39 publications

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“…Elevated levels of HA have been reported in patients with COPD (48), pulmonary fibrosis (49), and PAH (15,16). However, whether increased levels of HA are present in PH during COPD remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Collagen is one of many components of the lung ECM that is also composed of fibronectin, vitronectin, proteoglycans, and glycosaminoglycans (GAGs) (31). Of the GAGs, HA has been associated with idiopathic PH (16), and has also been reported to promote angiogenesis in models of lung fibrosis (32). To investigate whether HA was up-regulated in our mouse model of airspace enlargement and PH, transcript levels for HAS enzymes were evaluated according to RT-PCR.…”

Section: Lung Function In Adamentioning

confidence: 99%

“…Several mediators have been implicated in the development of PH secondary to COPD, such as endothelin-1 (13) and . In patients with idiopathic pulmonary arterial hypertension, the up-regulation of hyaluronan (HA), a major component of the lung ECM, has been associated with vascular remodeling (15,16). These observations are of interest, because HA has been shown to play an important role during inflammation and fibrosis (17).…”

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confidence: 99%

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Adenosine A2B Receptor and Hyaluronan Modulate Pulmonary Hypertension Associated with Chronic Obstructive Pulmonary Disease

Karmouty‐Quintana¹,

Weng

Garcia-Morales

et al. 2013

Am J Respir Cell Mol Biol

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Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide. The development of pulmonary hypertension (PH) in patients with COPD is strongly associated with increased mortality. Chronic inflammation and changes to the lung extracellular matrix (ECM) have been implicated in the pathogenesis of COPD, yet the mechanisms that lead to PH secondary to COPD remain unknown. Our experiments using human lung tissue show increased expression levels of the adenosine A 2B receptor (ADORA2B) and a heightened deposition of hyaluronan (HA; a component of the ECM) in remodeled vessels of patients with PH associated with COPD. We also demonstrate that the expression of HA synthase 2 correlates with mean pulmonary arterial pressures in patients with COPD, with and without a secondary diagnosis of PH. Using an animal model of airspace enlargement and PH, we show that the blockade of ADORA2B is able to attenuate the development of a PH phenotype that correlates with reduced levels of HA deposition in the vessels and the down-regulation of genes involved in the synthesis of HA.Keywords: adenosine; extracellular matrix; hyaluronic acid; remodeling; vascular Chronic obstructive pulmonary disease (COPD) is currently the fourth leading cause of death worldwide, and the World Health Organization predicts that it will become the third leading cause of death by 2030 (1). COPD is a heterogeneous disease characterized by airflow obstruction that is not fully reversible. Pathophysiological hallmarks of the disease include remodeling of the smallairway compartment, the loss of elastic recoil by emphysematous destruction of the parenchyma, inflammatory cell infiltration (2), and increased extracellular matrix (ECM) turnover (3). COPD is associated with a wide range of comorbidities, including ischemic heart disease, diabetes, skeletal muscle wasting, osteoporosis, and lung cancer (4). The development of pulmonary hypertension (PH) is a common and fatal complication in patients with COPD (5-7), and is strongly associated with decreased life expectancy (8).PH is a disorder of the pulmonary vasculature diagnosed by cardiac catheterization. PH is characterized by a mean pulmonary arterial pressure greater than or equal to 25 mm Hg that leads to right ventricular (RV) hypertrophy, followed by right-sided heart failure and death (9). Currently, treatment options are very limited for patients suffering from PH secondary to COPD (10, 11). Thus, to understand the mechanisms that lead to remodeling of the vasculature in COPD is important, with the hope of developing new treatment options for this fatal disorder.The pathogenesis of PH in COPD is a complex phenomenon characterized by extensive remodeling of the vasculature that results from an increased proliferation of pulmonary artery endothelial and smooth muscle cells, the muscularization of previously nonmuscular arteries, increased vascular tone, and the formation of complex vascular lesions (12). Factors involved in the development of PH in patients with COPD include ...

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Section: Discussionmentioning

confidence: 99%

Section: Lung Function In Adamentioning

confidence: 99%

mentioning

confidence: 99%

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Adenosine A2B Receptor and Hyaluronan Modulate Pulmonary Hypertension Associated with Chronic Obstructive Pulmonary Disease

Karmouty‐Quintana¹,

Weng

Garcia-Morales

et al. 2013

Am J Respir Cell Mol Biol

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“…ASMC were grown in Dulbecco modified Eagle medium supplemented with 5% fetal calf serum (FCS), 1% minimal essential medium vitamins, 8 mM stabilised Lglutamine and 10 mM HEPES buffer (GIBCO BRL; Life Technologies, Sydney, Australia). For all experiments, cells were used between passage four to nine; cells were grown until 80% confluence, and were serum deprived prior to H]-glucosamine into GAG was measured as previously described [23]. In brief, culture medium was collected and cells were washed twice with ice-cold PBS and lysed with 200 mL RIPA buffer (1% nonidet P-40, 1% sodium deoxycholate, 0.1% sodium dodecyl sulfate (SDS), 0.15 M NaCl, 0.01 M sodium phosphate, pH 7.2).…”

Section: Cell Culturesmentioning

confidence: 99%

Decreased hyaluronan in airway smooth muscle cells from patients with asthma and COPD

Klagas¹,

Goulet²,

Karakiulakis³

et al. 2009

European Respiratory Journal

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Glycosaminoglycans (GAG) are essential extracellular matrix molecules which regulate tissue flexibility, a parameter that is reduced in airways of patients with asthma and chronic obstructive pulmonary disease (COPD). We investigated the expression of GAG and their metabolising enzymes in primary human airway smooth muscle cells (ASMC) obtained from healthy donors (controls) and patients with asthma or COPD.Total GAG synthesis was assessed by [ 3 H]-glucosamine incorporation. GAG were isolated, purified, fractionated by electrophoresis and characterised using specific GAG-degrading enzymes. Secretion of hyaluronic acid (HA) by ASMC from patients with asthma or COPD was significantly decreased compared with controls. RT-PCR analysis and western blotting revealed that this decrease was associated with a significant reduction in the expression of HA synthase-1 and -2 and a significant increase of hyaluronidase-1. Furthermore, the expression of the HA receptor CD44 was significantly decreased, whereas the receptor for HA-mediated motility was not expressed in asthma or COPD.Our results indicate that there is a decreased expression of HA in asthma and COPD associated with a synergistic regulation of HA metabolising enzymes that may regulate the pathological airway remodelling in these lung diseases.

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“…[37] HA is mainly produced by mesenchymal cells but can also be produced by other cell types. [38][39][40][41][42][43] It keeps the body smooth, moist and lubricated. During aging, HA present in the skin diminishes leading to the dry and wrinkled skin.…”

Section: Hyaluroinidasesmentioning

confidence: 99%

Untitled

Garg

2017

IJGP

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Skin ageing is a complex multifactorial process occurring in all living beings. It generally comprises two independent and distinct processes, i.e., intrinsic, age-dependent or chronological aging and premature aging, or photoaging which is the result of undue exposure of the skin to ultraviolet (UV) radiations. Photoaging can be prevented or the effects of photoaging can be reduced by the use of certain anti-aging and anti-wrinkle agents. The extracellular matrix (ECM) which forms the outermost part of skin comprises fibroblasts and proteins such as collagen and elastin. Degradation of ECM is directly linked to skin aging and is responsible for the increase in activity of certain enzymes such as collagenase, elastase, and hyaluronidase (HYAL) that are involved in skin aging. With aging there is decrease in the levels of elastin, collagen, and hyaluronic acid which leads to loss of strength and flexibility of skin and appear as wrinkles on the skin. Further, the increase in the activity of collagenase, elastase, and HYAL is triggered by the high levels of reactive oxygen species produced when the skin is exposed to excessive UV radiations leading to skin aging. Today, in the age of modern science and advanced technology, although many techniques such as laser rejuvenation, plastic surgery, and lots of synthetic products such as sunscreen lotions, creams are available yet, there is a place for natural, herbal anti-aging cosmetics. Various botanical extracts have the power to reduce the appearance of skin aging and enhance the beauty of the skin. Medicinal plants have several phytoconstituents such as polyphenols, alkaloids, tannins, saponins, carotenoids, and terpenoids which possess antioxidant properties and can be used in treating the signs of aging. Some plants contain phenolic compounds which have free-radical scavenging property and can suppress aging. Some plants or their extracts possess several other constituents that may have the capability of inhibiting various enzyme such as HYAL, elastase, and matrix metalloproteinases enzyme that play a major role in skin aging. Some of them may possess the free radical scavenging or antioxidant property to fight against the signs of aging. This review focuses on the compilation of medicinal plants and natural compounds as anti-aging and anti-wrinkling agents along with their chemical constituents based on their possible molecular mechanism of action. The present review will facilitate the scientists working in this area for the development of new anti-aging and anti-wrinkle formulations with better efficiency and safety.

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Increased hyaluronic acid content in idiopathic pulmonary arterial hypertension

Cited by 51 publications

References 39 publications

Adenosine A2B Receptor and Hyaluronan Modulate Pulmonary Hypertension Associated with Chronic Obstructive Pulmonary Disease

Adenosine A2B Receptor and Hyaluronan Modulate Pulmonary Hypertension Associated with Chronic Obstructive Pulmonary Disease

Decreased hyaluronan in airway smooth muscle cells from patients with asthma and COPD

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