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Introduction Pulmonary arterial hypertension classification and prevalence Pulmonary hypertension (PH) refers to 5 subgroups of progressive cardiopulmonary disorders characterized by a combination of idiopathies, genetic variants, and environmental factors that [...], Pulmonary arterial hypertension (PAH) is a devastating disease of the cardiopulmonary system caused by the narrowing of the pulmonary arteries, leading to increased vascular resistance and pressure. This leads to right ventricle remodeling, dysfunction, and eventually, death. While conventional therapies have largely focused on targeting vasodilation, other pathological features of PAH including aberrant inflammation, mitochondrial dynamics, cell proliferation, and migration have not been well explored. Thus, despite some recent improvements in PAH treatment, the life expectancy and quality of life for patients with PAH remains poor. Showing many similarities to cancers, PAH is characterized by increased pulmonary arterial smooth muscle cell proliferation, decreased apoptotic signaling pathways, and changes in metabolism. The recent successes of therapies targeting epigenetic modifiers for the treatment of cancer has prompted epigenetic research in PAH, revealing many new potential therapeutic targets. In this minireviewwe discuss the emergence of epigenetic dysregulation in PAH and highlight epigenetic-targeting compounds that may be effective for the treatment of PAH. Key words: pulmonary arterial hypertension, epigenetics, clinical trial. L'hypertension arterielle pulmonaire (HAP) est une maladie devastatrice du systeme cardiopulmonaire provoquee par le retrecissement des arteres pulmonaires, ce qui entraine une augmentation de la resistance et de la pression vasculaires. Cela conduit a un remodelage et un dysfonctionnement du ventricule droit, et eventuellement, a la mort. Alors que les therapies conventionnelles se sont largement concentrees sur la vasodilatation, d'autres caracteristiques pathologiques de l'HAP, notamment l'inflammation aberrante, la dynamique mitochondriale, la proliferation et la migration des cellules, n'ont pas ete bien explorees. Ainsi, malgre certaines ameliorations recentes dans le traitement de l'HAP, l'esperance et la qualite de vie des patients qui en sont atteints demeurent faibles. Presentant de nombreuses similitudes avec le cancer, l'HAP est caracterisee par un accroissement de la proliferation des cellules musculaires lisses arterielles pulmonaires, une diminution des voies de signalisation apoptotiques et des changements dans le metabolisme. Les recents succes des therapies qui ciblent des modificateurs epigenetiques dans le traitement de cancer ont encourage la recherche en epigenetique dans l'HAP, revelant plusieurs nouvelles cibles therapeutiques potentielles. Dans cette synthese, les auteurs discutent de l'emergence de la dysregulation epigenetique dans l'HAP et mettent en evidence des composes qui ciblent l'epigenetique qui pourraient etre efficaces dans le traitement de l'HAP. [Traduit par la Redaction] Mots-cles: hypertension arterielle pulmonaire, epigenetique, essai clinique.

Soil CO fluxes represent a net balance between biological soil CO uptake and abiotic soil and (senescent) plant CO production. Studies largely from temperate and boreal forests indicate that soils serve as a net sink for CO, but to date uncertainty remains about the role of tropical rain forest soils. Here we report the first direct measurements of soil CO fluxes in a tropical rain forest. We compare with estimates of net ecosystem CO fluxes derived from accumulation of CO at night under stable atmospheric conditions. Further, we used laboratory experiments to demonstrate the importance of temperature on net soil CO fluxes. Net soil surface CO fluxes ranged from -0.19 to 3.36 nmol m-2 s-1, averaging ∼1 nmol CO m-2 s-1. Fluxes varied with season and topographic location, with highest fluxes measured in the dry season in a seasonally inundated valley. Ecosystem CO fluxes estimated from nocturnal canopy air profiles, which showed CO mixing ratios that consistently decreased with height, ranged between 0.3 and 2.0 nmol CO m-2 s-1. A canopy layer budget method, using the nocturnal increase in CO, estimated similar flux magnitudes (1.1 to 2.3 nmol CO m-2 s-1). In the wet season, a greater valley ecosystem CO production was observed in comparison to measured soil valley CO fluxes, suggesting a contribution of the valley stream to overall CO emissions. Laboratory incubations demonstrated a clear increase in CO production with temperature that was also observed in field fluxes, though high correlations between soil temperature and moisture limit our ability to interpret the field relationship. At a common temperature (25 ◦C), expected plateau and valley senescent leaf CO production was small (0.012 and 0.002 nmol CO m-2 s-1) in comparison to expected soil material CO emission (∼0.9 nmol CO m-2 s-1). Based on our field and laboratory observations, we expect that tropical rain forest ecosystems are a net source of CO, with thermal degradation-induced soil emissions likely being the main contributor to ecosystem CO emissions. Extrapolating our first observation-based tropical rain forest soil emission estimate of ∼1 nmol m-2 s-1, a global tropical rain forest soil emission of ∼16.0 Tg CO yr-1 is estimated. Nevertheless, total ecosystem CO emissions might be higher, since valley streams and inundated areas might represent local CO emission hot spots. To further improve tropical forest ecosystem CO emission estimates, more in-situ tropical forest soil and ecosystem CO flux measurements are essential. [ABSTRACT FROM AUTHOR]

Soil CO fluxes represent a net balance between biological soil CO uptake and abiotic soil and (senescent) plant CO production. Studies largely from temperate and boreal forests indicate that soils serve as a net sink for CO, but to date uncertainty remains about the role of tropical rain forest soils. Here we report the first direct measurements of soil CO fluxes in a tropical rain forest. We compare with estimates of net ecosystem CO fluxes derived from accumulation of CO at night under stable atmospheric conditions. Further, we used laboratory experiments to demonstrate the importance of temperature on net soil CO fluxes. Net soil surface CO fluxes ranged from -0.19 to 3.36 nmol m-2 s-1, averaging ∼1 nmol CO m-2 s-1. Fluxes varied with season and topographic location, with highest fluxes measured in the dry season in a seasonally inundated valley. Ecosystem CO fluxes estimated from nocturnal canopy air profiles, which showed CO mixing ratios that consistently decreased with height, ranged between 0.3 and 2.0 nmol CO m-2 s-1. A canopy layer budget method, using the nocturnal increase in CO, estimated similar flux magnitudes (1.1 to 2.3 nmol CO m-2 s-1). In the wet season, a greater valley ecosystem CO production was observed in comparison to measured soil valley CO fluxes, suggesting a contribution of the valley stream to overall CO emissions. Laboratory incubations demonstrated a clear increase in CO production with temperature that was also observed in field fluxes, though high correlations between soil temperature and moisture limit our ability to interpret the field relationship. At a common temperature (25 °C), expected plateau and valley senescent leaf CO production was small (0.012 and 0.002 nmol CO m-2 s-1) in comparison to expected soil material CO emission (∼0.9 nmol CO m-2 s-1). Based on our field and laboratory observations, we expect that tropical rain forest ecosystems are a net source of CO, with thermal degradation-induced soil emissions likely being the main contributor to ecosystem CO emissions. Extrapolating our first observation-based tropical rain forest soil emission estimate of ∼1 nmol m-2 s-1, a global tropical rain forest soil emission of ∼16.0 Tg CO yr-1 is estimated. Nevertheless, total ecosystem CO emissions might be higher, since valley streams and inundated areas might represent local CO emission hot spots. To further improve tropical forest ecosystem CO emission estimates, more in-situ tropical forest soil and ecosystem CO flux measurements are essential. [ABSTRACT FROM AUTHOR]