Effect of Sacubitril-Valsartan on Transcriptomic Changes in Lung Tissue of Spontaneously Hypertensive Rats: A...

Area of Science:

• Cardiovascular Research
• Pulmonary Medicine
• Molecular Biology

Background:

• Hypertension is a common cardiovascular disease with known adverse effects on the respiratory system.
• The precise molecular mechanisms linking hypertension to pulmonary damage are not fully understood.

Purpose of the Study:

• To investigate the molecular changes in lung tissue associated with hypertension.
• To compare the effects of Angiotensin Receptor Blocker (ARB) and Angiotensin Receptor-Neprilysin Inhibitor (ARNI) therapies on hypertension-induced pulmonary alterations.

Main Methods:

• Comparative transcriptomic profiling using RNA sequencing (RNA-seq) on lung tissues from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) controls.
• Integrated omics approaches to analyze mRNA and protein expression profiles in SHR pulmonary tissue following ARB and ARNI interventions.

Main Results:

• Key differentially expressed genes (DEGs) in SHR vs. WKY included Nuf2 and Cenpa, with enrichment in the PI3K/AKT signaling pathway.
• ARB treatment highlighted hub genes Ccnb2 and Mad2l1 involved in cell cycle regulation and HTLV-1 infection.
• ARNI treatment identified hub genes Gzma and Icam1, enriched in PI3K/AKT signaling and extracellular matrix (ECM)-receptor interactions.
• Proteomic analysis corroborated transcriptomic findings for EGFR and JUN proteins.

Conclusions:

• Both ARB and ARNI therapies demonstrate efficacy in mitigating hypertension-induced pulmonary damage.
• These therapies operate through distinct molecular pathways.
• PI3K/AKT signaling and ECM-receptor interactions are identified as crucial regulatory hubs in the protective effects of these treatments.