ABSTRACT
Background:
Hypertrophic cardiomyopathy (HCM), identified as a primary cause of
sudden cardiac death (SCD), intertwines with
pulmonary hypertension (
PH) to amplify cardiovascular
morbidity. This complex synergy poses significant
therapeutic challenges due to the absence of
drugs specifically targeting their concurrent manifestation. This study seeks to unravel the molecular intricacies linking HCM and
PH, aiming to lay the groundwork for targeted
therapeutic interventions.
Methods:
Through the
analysis of
gene expression profiles from datasets GSE36961 (HCM) and GSE113439 (
PH) within the public data repository of
Gene Expression Omnibus (GEO), this
research systematically identified differentially expressed
genes (DEGs), conducted extensive functional annotations, and constructed detailed
protein-
protein interaction (PPI) networks to uncover crucial hub
genes. Further, co-expression analyses, alongside
drug prediction and
molecular docking simulations, were employed to pinpoint potential
therapeutic agents that could ameliorate the combined
pathology of HCM and
PH.
Results:
Our comprehensive
analysis unearthed 79 DEGs
shared between HCM and
PH, highlighting fourteen as pivotal hub
genes. Validation across three additional datasets (GSE35229, GSE32453, and GSE53408) from GEO accentuated
secreted phosphoprotein 1 (SPP1) as a key
gene of interest. Remarkably, the study identified
tacrolimus, ponatinib, bosutinib,
dasatinib,
doxorubicin, and zanubrutinib as promising
drugs for addressing the dual challenge of HCM and
PH.
Conclusions:
The findings of this investigation shed
light on the genetic underpinnings of HCM and
PH's simultaneous occurrence, emphasizing the central
role of SPP1 in their pathogenesis. The identification of six candidate
drugs offers a hopeful vista for
future therapeutic strategies targeting this complex cardiovascular interplay, marking a significant stride towards mitigating the compounded
morbidity of HCM and
PH.
Future mechanistic and clinical studies are warranted for the investigation of this potential target and
therapeutics.