Transcriptome of hypertension-induced left ventricular hypertrophy and its regression by antihypertensive therapies

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Hypertension Research

Background:

• Left ventricular hypertrophy (LVH) is a common, detrimental consequence of systemic hypertension.
• LVH is a potentially reversible condition, but the molecular mechanisms underlying its regression remain incompletely understood.
• Understanding gene expression changes during LVH development and regression is crucial for effective therapeutic strategies.

Purpose of the Study:

• To investigate the molecular pathways involved in the development of LVH.
• To analyze how antihypertensive regimens modulate these pathways during LVH regression.
• To identify persistent gene expression alterations after successful LVH reversal.

Main Methods:

• Utilized spontaneously hypertensive rats (SHR) at early and late stages of LVH, with normotensive Wistar-Kyoto rats as controls.
• Administered three antihypertensive regimens: quinapril, a combination of doxazosin and quinapril, and losartan for 36 weeks.
• Performed gene expression profiling using Affymetrix microarrays and hierarchical cluster analysis.

Main Results:

• Significant alterations in gene expression were observed in early (1.9%) and late (0.9%) LVH compared to controls.
• Predominant changes occurred in metabolism, cell growth, signal transduction, development, and muscle contraction pathways.
• Despite significant LVH regression, 31 LVH-associated transcripts remained unchanged by any treatment, indicating incomplete transcriptome normalization.

Conclusions:

• Regression of hypertension-induced LVH does not fully normalize the cardiac transcriptome.
• Antihypertensive treatments induce distinct gene expression profiles, even when achieving LVH regression.
• LVH regression is associated with a unique gene expression profile, suggesting persistent myocardial adaptations beyond the direct effects of treatment.