[Pulmonary hypertension in rheumatic diseases]

Area of Science:

• Cardiovascular Medicine
• Genetics
• Rheumatology

Background:

• Pulmonary hypertension (PH) is a progressive vascular disease characterized by elevated pulmonary vascular resistance and right ventricle pressure overload.
• Histological hallmarks include medial hypertrophy of pulmonary arteries and endothelial cell proliferation forming plexiform lesions.
• Genetic factors, such as mutations in BMPR2 and ALK1 genes within the TGF-beta superfamily, are implicated in PH pathogenesis.

Purpose of the Study:

• To explore the underlying mechanisms of pulmonary vascular disease in rheumatic conditions.
• To understand the role of genetic mutations and other factors in the multi-hit process of PH development.
• To review the association of PH with systemic sclerosis (SS), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD).

Main Methods:

• Review of recent studies identifying gene mutations (BMPR2, ALK1) affecting the TGF-beta receptor superfamily.
• Analysis of evidence suggesting a multi-hit model for PH development involving genetic and environmental factors.
• Examination of the prevalence and mechanisms of PH in rheumatic diseases like SS, SLE, and MCTD.

Main Results:

• Mutations in BMPR2 and ALK1 genes, part of the TGF-beta receptor superfamily, are linked to PH.
• PH development is considered a multi-hit process, potentially involving gene mutations combined with other conditions or genes.
• PH is a rare but recognized complication of systemic sclerosis (approx. 10% of cases), SLE, and MCTD.

Conclusions:

• Genetic predispositions, such as BMPR2 mutations, play a role in PH.
• The exact mechanisms driving PH in rheumatic diseases remain unclear.
• Symptomatic vasodilator therapies can improve exercise capacity and survival in PH patients.