Pathogenic Mechanisms of Pulmonary Arterial Hypertension

Pulmonary Hypertension and Hyperglycemia—Not a Sweet Combination

“…When a diagnosis of PAH is made in elderly patients who present with cardiovascular comorbidities such as diabetes mellitus and obesity, early identification and treatment of PAH can improve outcomes. Endothelial dysfunction, a common denominator in both conditions, plays a pivotal role in their pathogenesis [1,11,12]. Endo-…”

“…Inflammatory mediators such as cytokines, chemokines, and growth factors contribute to endothelial injury, smooth muscle cell proliferation, and fibrosis in the pulmonary vasculature [1,11]. Several common inflammatory mediators play pivotal roles in both pulmonary hypertension (PH) and metabolic pathways, contributing to the interconnection between impaired glucose metabolism and PH [11,12]. Some of the key inflammatory mediators (see Table 1) involved include: The cytokine tumor necrosis factor-α (TNF-α), and its receptors, 1 and 2 (TNFR1, TNFR2), are members of TNFR superfamily, and are important mediators of chronic inflammation in diabetes mellitus [14,15].…”

“…Recent studies have suggested a bidirectional relationship between PH and hyperglycemia [ 4 , 8 , 11 ]. When a diagnosis of PAH is made in elderly patients who present with cardiovascular comorbidities such as diabetes mellitus and obesity, early identification and treatment of PAH can improve outcomes.…”

“…When a diagnosis of PAH is made in elderly patients who present with cardiovascular comorbidities such as diabetes mellitus and obesity, early identification and treatment of PAH can improve outcomes. Endothelial dysfunction, a common denominator in both conditions, plays a pivotal role in their pathogenesis [ 1 , 11 , 12 ]. Endothelial injury and inflammation contribute to vascular remodeling and vasoconstriction in PH, and decreased endothelium-dependent vasodilation and hyperpermeability, is the initial stage of vasculopathy.…”

“…Both DM and PH are characterized by endothelial dysfunction, marked by impaired nitric oxide bioavailability, increased oxidative stress, and inflammation [ 1 , 11 , 12 ]. Endothelial dysfunction contributes to vasoconstriction, vascular remodeling, and thrombosis in the pulmonary vasculature, exacerbating PH vasculopathy.…”