In this review, we examine the molecular mechanisms underlying the hypoxia-pulmonary hypertension axis, focusing on the complex and interconnected signaling networks involving redox imbalance, PI3K–Akt signaling, Na+/H+ exchange, nitric oxide bioavailability, autophagy, mitochondrial dynamics and mitophagy, metabolic reprogramming, inflammation, adventitial remodeling with particular emphasis on pulmonary arterial adventitial fibroblasts, and erythropoietin signaling. This evidence concerns the gene AKT1 and pulmonary arterial hypertension.