Pulmonary Arterial Hypertension with Senescence

Sunena Williams^*
*Correspondence: Sunena Williams, Division of Pulmonary, Critical Care and Sleep Medicine, Stony Brook University, New york, USA, Email:

Editorial

The term "pulmonary hypertension" refers to a group of illnesses, including pulmonary arterial hypertension (PAH) (PH). A precapillary portion of the pulmonary vasculature has a special pathobiology role in PAH, which exhibits a distinctive hemodynamic pattern during right heart catheterization. It is still recognised as a progressive disease with a poor prognosis despite recent advancements in treatment. PAH can be idiopathic or accompanied with other disorders, although pulmonary vasculopathy is always the first pathogenetic lesion [1]. Right ventricular failure and mortality result from progressive obstructive arteriopathy, which first affects the medial-to-small pulmonary arteries.

When a rise in the pressure within the pulmonary circulation results from some underlying illnesses, such as lung or heart disease, this is distinct from the other types of PH. Endothelial cell malfunction, unchecked proliferation of vascular smooth muscle cells and fibroblasts, adventitial fibrosis development, and inflammatory cell infiltration are some of the molecular pathways underlying vascular remodelling in PAH.

PAH has typically been identified as a condition affecting young women. Evidence is mounting that it is now more frequently observed in older age groups as well. According to data from the registry including many European nations, up to 63 percent of patients in a cohort with PAH were over 65. The Swiss registry's data revealed that the average age of PAH a patient is 60 years old. 9-13.5 percent of those with PAH are older than 70 years old, according to data from both the US and European registries. As a result, the majority of PAH patients today are middle-aged or older adults, and the mechanisms associated with normal ageing may have an impact on how the illness progresses in these patients.

The pulmonary artery is known to harden as people age due to changes in the pulmonary vasculature. Additionally, it is known that systolic pulmonary arterial pressure rises by 1 mmHg every decade as people age. Normal ageing is accompanied by changes in lung elastic recoil, stiffness of the chest wall, strength of the respiratory muscles, and lung capillary loss, all of which contribute to an increase in pulmonary vascular resistance and pulmonary artery pressure [2,3]. In addition to being more often obese, older persons with PAH are more likely to have concomitant conditions such hypertension, ischemic heart disease, atrial fibrillation, and chronic obstructive pulmonary disease, all of which can directly result in PH. Therefore, pulmonary hemodynamics is significantly influenced by biological age. Age also increases the pulmonary artery pressure, complicating the diagnosis of PAH and possibly affecting how the disease develops. Age is a risk factor for various diseases. Even with the use of contemporary medications, elderly PAH patients have been proven to have more severe pulmonary vasculopathy and generally have lower survival rates.

The buildup of senescent cells in many organs and tissues has been connected to chronobiologic ageing. Despite being previously believed to be metabolically dormant, it has been demonstrated that these cells display a senescence-associated secretory phenotype (SASP), which is characterised by the release of remodelling proteins, pro-inflammatory cytokines, and other substances that, in a paracrine/autocrine manner, promote metabolic dysfunction. The milieu that encourages tissue deterioration and functional decline in numerous organs as we age is known to be formed in large part by the senescence-associated secretory phenotype (SASP). Senescent cell buildups at the sites of pathogenesis and their bioactive secretome have both been postulated to have a role in the pathobiology of many chronic diseases. Senescent endothelial cells that are concentrated in the brittle plaque of human atherosclerotic lesions cause endothelial dysfunction by reducing nitric oxide and prostacyclin production [4]. Further promoting vascular dysfunction in many cardiovascular illnesses is proinflammatory and profibrotic SASP, which is produced by ageing endothelium and vascular smooth muscle cells.

In the treatment of PAH, the pharmacological agents that target cellular senescence and SASP are of particular interest. Senolytics, which lessen the burden of senescent cells by inducing their apoptosis, SASP inhibitors, which combat the pro-inflammatory and profibrotic effects of senescent cells, and geroprotectors, which prevent the formation of senescent cells by limiting the effects of various stressors, primarily oxidative stressors, make up the current arsenal of senotherapy [5]. In PAH models, various substances that target (pro)-antiapoptotic pathways and, hence, fit the concept of a senolytic, were evaluated.

The pyrrolizidine alkaloid monocrotaline (see above) and the vascular endothelial growth factor inhibitor Sugen 5416, which are used to induce pulmonary vascular remodelling in animal studies, actually cause premature cellular senescence by producing too many reactive oxygen species, which causes DNA damage. Additionally, dietary substances like quercetin and other polyphenols that may aid in the pharmacotherapy of PAH are being researched for their senolytic effect in lung disease.

Conflict of Interest

The author declares that there is no conflict of interest associated with this manuscript.

References

1. Semen, Khrystyna O., and Aalt Bast. "Senescence in pulmonary arterial hypertension: is there a link?." Curr Opin Pulm Med 28 (2022): 303-306.

Google Scholar, Crossref, Indexed at

2. Van Der Feen, Diederik E., Guido PL Bossers, and Quint AJ Hagdorn, et al. "Cellular senescence impairs the reversibility of pulmonary arterial hypertension." Sci Transl Med 12 (2020): eaaw4974.

Google Scholar, Crossref, Indexed at

3. Roger, Inés, Javier Milara, Nada Belhadj, and Julio Cortijo. "Senescence Alterations in Pulmonary Hypertension." Cells 10 (2021): 3456.

Google Scholar, Crossref, Indexed at

4. Chen, Maggie S., Richard T. Lee, and Jessica C. Garbern. "Senescence mechanisms and targets in the heart." Cardiovasc Res 118 (2022): 1173-1187.

Google Scholar, Crossref, Indexed at

5. Born, Emmanuelle, Larissa Lipskaia, Shariq Abid, and Amal Houssaini, et al. "Cell senescence in pulmonary hypertension." Cell  Senescence  Dis (2022): 81-105.

Google Scholar, Crossref