<scp>PDE5</scp> to keep them alive: The use of phosphodiesterase type‐5 inhibitors in severe pulmonary hypertension associated with interstitial lung disease

Weatherald, Jason; Humbert, Marc

doi:10.1111/resp.14399

Cited by 2 publications

(1 citation statement)

References 13 publications

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“…Later, two other PDE-5 inhibitor studies with sildenafil published in 2018 ( 54 ) and 2021 ( 55 ) failed to show any significant effect. However, those studies were limited by lack of PH confirmation by RHC ( 56 ). The selection bias of potentially including non-PH patients may have produced a type-II error.…”

Section: Management: Light At the End Of The Tunnel!mentioning

confidence: 99%

Evolution of pulmonary hypertension in interstitial lung disease: a journey through past, present, and future

Arslan,

Smith,

Qureshi

et al. 2024

Front. Med.

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Interstitial lung diseases (ILD) are a spectrum of disorders often complicated by pulmonary hypertension (PH) in its course. The pathophysiologic mechanism of WHO group 3 PH is different to other forms of PH. The advent of PH is a harbinger for adverse events like mortality and morbidity, implying that the PH component of disease expedites deteriorated clinical outcomes. In fact, WHO group 3 PH due to ILD has the worse prognosis among all groups of PH. Hence, early detection of PH by a comprehensive screening method is paramount. Given considerable overlap in clinical manifestations between ILD and PH, early detection of PH is often elusive. Despite, the treatment of PH due to ILD has been frustrating until recently. Clinical trials utilizing PAH-specific pulmonary vasodilators have been ongoing for years without desired results. Eventually, the INCREASE study (2018) demonstrated beneficial effect of inhaled Treprostinil to treat PH in ILD. In view of this pioneering development, a paradigm shift in clinical approach to this disease phenotype is happening. There is a renewed vigor to develop a well validated screening tool for early detection and management. Currently inhaled Treprostinil is the only FDA approved therapy to treat this phenotype, but emergence of a therapy has opened a plethora of research toward new drug developments. Regardless of all these recent developments, the overall outlook still remains grim in this condition. This review article dwells on the current state of knowledge of pre-capillary PH due to ILD, especially its diagnosis and management, the recent progresses, and future evolutions in this field.

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Section: Management: Light At the End Of The Tunnel!mentioning

confidence: 99%

Evolution of pulmonary hypertension in interstitial lung disease: a journey through past, present, and future

Arslan,

Smith,

Qureshi

et al. 2024

Front. Med.

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miR‐30d Attenuates Pulmonary Arterial Hypertension via Targeting MTDH and PDE5A and Modulates the Beneficial Effect of Sildenafil

Liang,

Zhou,

Wang

et al. 2024

Advanced Science

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Pulmonary arterial hypertension (PAH) is associated with aberrant pulmonary vascular smooth muscle cell (PASMC) function and vascular remodeling. MiR‐30d plays an important role in the pathogenesis of several cardiovascular disorders. However, the function of miR‐30d in PAH progression remained unknown. Our study shows that circulating miR‐30d level is significantly reduced in the plasma from PAH patients. In miR‐30d transgenic (TG) rats, overexpressing miR‐30d attenuates monocrotaline (MCT)‐induced pulmonary hypertension (PH) and pulmonary vascular remodeling. Increasing miR‐30d also inhibits platelet‐derived growth factor‐bb (PDGF‐bb)‐induced proliferation and migration of human PASMC. Metadherin (MTDH) and phosphodiesterase 5A (PDE5A) are identified as direct target genes of miR‐30d. Meanwhile, nuclear respiratory factor 1 (NRF1) acts as a positive upstream regulator of miR‐30d. Using miR‐30d knockout (KO) rats treated with sildenafil, a PDE5A inhibitor that is used in clinical PAH therapies, it is further found that suppressing miR‐30d partially attenuates the beneficial effect of sildenafil against MCT‐induced PH and vascular remodeling. The present study shows a protective effect of miR‐30d against PAH and pulmonary vascular remodeling through targeting MTDH and PDE5A and reveals that miR‐30d modulates the beneficial effect of sildenafil in treating PAH. MiR‐30d should be a prospective target to treat PAH and pulmonary vascular remodeling.

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PDE5 to keep them alive: The use of phosphodiesterase type‐5 inhibitors in severe pulmonary hypertension associated with interstitial lung disease

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Cited by 2 publications

References 13 publications

Evolution of pulmonary hypertension in interstitial lung disease: a journey through past, present, and future

Evolution of pulmonary hypertension in interstitial lung disease: a journey through past, present, and future

miR‐30d Attenuates Pulmonary Arterial Hypertension via Targeting MTDH and PDE5A and Modulates the Beneficial Effect of Sildenafil

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