Key result
Disease heterogeneity limits translation of molecular and genetic advances into pulmonary hypertension clinical practice.
Why the study?
Existing cardiovascular biomarkers have low specificity in pulmonary hypertension due to comorbidities, and clinical translation of novel molecular targets remains difficult given the marked pathophysiological heterogeneity of the disease.
This review highlights the complex molecular pathophysiology of pulmonary hypertension, emphasizing the role of genetic mutations and epigenetic modifications as potential novel biomarkers and therapeutic targets.
Answers are grounded in this paper and cite their sources.
Despite molecular advances, PH heterogeneity limits clinical translation; leaves open validation of genetic and epigenetic targets as biomarkers.
Pulmonary hypertension (PH) is defined as increased mean pulmonary artery pressure (mPAP) above 25 mmHg, measured at rest by right heart catheterization. The exact global prevalence of PH is difficult to estimate, mainly due to the complex aetiology, and its spread may be underestimated. To date, numerous studies on the aetiology and pathophysiology of PH at molecular level were conducted. Simultaneously, some clinical studies have shown potential usefulness of well-known and widely recognized cardiovascular biomarkers, but their potential clinical usefulness in diagnosis and management of PH is poor due to their low specificity accompanied with numerous other cardiovascular comorbidities of PH subjects. On the other hand, a large body of basic research-based studies provides us with novel molecular pathomechanisms, biomarkers, and drug targets, according to the evidence-based medicine principles. Unfortunately, the simple implementation of these results to clinical practice is impossible due to a large heterogeneity of the PH pathophysiology, where the clinical symptoms constitute only a common denominator and a final result of numerous crosstalking metabolic pathways. Therefore, future studies, based mostly on translational medicine, are needed in order to both organize better the pathophysiological classification of various forms of PH and define precisely the optimal diagnostic markers and therapeutic targets in particular forms of PH. This review paper summarizes the current state of the art regarding the molecular background of PH with respect to its current classification. Novel therapeutic strategies and potential biomarkers are discussed with respect to their limitations in use in common clinical practice.
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Gajecki et al. (2020) conducted a review in Pulmonary hypertension. This review highlights that despite advances in understanding the molecular, genetic, and metabolic mechanisms of pulmonary hypertension, translating these findings into clinical practice remains challenging due to disease heterogeneity.
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