Pyelonephritis decreases serum cholesterol and mitigates atherosclerosis severity despite systemic inflammation

Area of Science:

• Cardiovascular Disease Research
• Renal Pathology
• Immunology

Background:

• Hypercholesterolemia and inflammation are key drivers of cardiovascular disease.
• Urinary tract infections, particularly pyelonephritis, are common and recurrent.
• The impact of pyelonephritis on atherosclerosis and lipid profiles remains incompletely understood.

Purpose of the Study:

• To investigate the effects of pyelonephritis on atherosclerotic plaque development and lipid levels.
• To explore the underlying mechanisms, including gene regulation and immune cell involvement.
• To correlate findings in animal models with human patient data.

Main Methods:

• Utilized LDL receptor deficient (Ldlr-/-) and wildtype mice infected with uropathogenic E. coli.
• Assessed renal and systemic inflammation, lipid levels, and atherosclerotic lesion size.
• Analyzed gene expression in kidneys and human cells; studied patient cohorts with urinary tract infections.

Main Results:

• Chronic pyelonephritis induced systemic inflammation, anemia, and neutrophilia.
• Atherosclerotic lesion size in Ldlr-/- mice tended to be smaller, correlating with decreased serum cholesterol and increased neutrophil counts.
• Renal gene expression related to cholesterol homeostasis and fatty acid metabolism was altered, with neutrophil involvement confirmed in vitro and in patients.

Conclusions:

• Bacterial kidney infection leads to decreased serum cholesterol and offers relative protection against atherosclerosis despite severe systemic inflammation.
• Neutrophils play a role in regulating renal cholesterol metabolism during pyelonephritis.
• This study reveals a novel mechanism linking infection, inflammation, and lipid metabolism in cardiovascular disease pathogenesis.