Genetic Delivery and Gene Therapy in Pulmonary Hypertension.
Nabham RaiMazen ShihanWerner SeegerRalph T SchermulyTatyana NovoyatlevaPublished in: International journal of molecular sciences (2021)
Pulmonary hypertension (PH) is a progressive complex fatal disease of multiple etiologies. Hyperproliferation and resistance to apoptosis of vascular cells of intimal, medial, and adventitial layers of pulmonary vessels trigger excessive pulmonary vascular remodeling and vasoconstriction in the course of pulmonary arterial hypertension (PAH), a subgroup of PH. Multiple gene mutation/s or dysregulated gene expression contribute to the pathogenesis of PAH by endorsing the proliferation and promoting the resistance to apoptosis of pulmonary vascular cells. Given the vital role of these cells in PAH progression, the development of safe and efficient-gene therapeutic approaches that lead to restoration or down-regulation of gene expression, generally involved in the etiology of the disease is the need of the hour. Currently, none of the FDA-approved drugs provides a cure against PH, hence innovative tools may offer a novel treatment paradigm for this progressive and lethal disorder by silencing pathological genes, expressing therapeutic proteins, or through gene-editing applications. Here, we review the effectiveness and limitations of the presently available gene therapy approaches for PH. We provide a brief survey of commonly existing and currently applicable gene transfer methods for pulmonary vascular cells in vitro and describe some more recent developments for gene delivery existing in the field of PH in vivo.
Keyphrases
- pulmonary hypertension
- cell cycle arrest
- pulmonary arterial hypertension
- induced apoptosis
- gene expression
- gene therapy
- endoplasmic reticulum stress
- pulmonary artery
- cell death
- pi k akt
- multiple sclerosis
- randomized controlled trial
- dna methylation
- blood pressure
- cell proliferation
- coronary artery
- physical activity
- transcription factor
- polycyclic aromatic hydrocarbons