Age-Related Differential Structural and Transcriptomic Responses in the Hypertensive Heart

Area of Science:

• Cardiovascular Science
• Aging Research
• Hypertension Studies

Background:

• Aging is a primary risk factor for heart failure.
• The aging heart's response to hypertensive stimuli is not fully understood.
• Investigating age-related differences in cardiac response to hypertension is crucial for understanding cardiovascular disease.

Purpose of the Study:

• To investigate phenotypic and transcriptomic differences between young and aging hearts under hypertensive conditions.
• To compare the cardiac response to a mineralocorticoid-excess model of hypertension in young versus aging mice.
• To identify molecular pathways altered by hypertension in aging hearts.

Main Methods:

• Utilized a mineralocorticoid-excess model (deoxycorticosterone acetate - DOCA) in young (10-week) and aging (36-week) mice.
• Assessed cardiac structure, function, blood pressure, and cardiac transcriptome over 6 weeks.
• Employed unilateral nephrectomy and DOCA pellet implantation for hypertension induction.

Main Results:

• Both young and aging DOCA mice exhibited elevated blood pressure, cardiac mass, hypertrophy, and fibrosis.
• Aging DOCA mice showed increased left ventricular end-diastolic pressure and greater perivascular fibrosis compared to young DOCA mice.
• Transcriptomic analysis revealed higher oxidative stress in young mice and increased collagen formation, innate immunity, and inflammation in aging mice.

Conclusions:

• Aging hearts exhibit distinct phenotypic and molecular responses to hypertensive stress compared to younger hearts.
• Hypertension in aging mice is associated with enhanced fibrosis, inflammation, and immune system activation.
• These findings highlight potential mechanisms contributing to age-related cardiovascular diseases, particularly heart failure.