Cysteinyl cathepsins in cardiovascular diseases

Area of Science:

• Biochemistry
• Molecular Biology
• Cardiology

Background:

• Cysteinyl cathepsins are proteases primarily located in lysosomes/endosomes.
• These enzymes are increasingly found outside their typical compartments, including the nucleus, cytosol, and extracellular space.
• Elevated cathepsin levels in plasma and cardiac tissue are observed in patients with cardiovascular diseases (CVD).

Purpose of the Study:

• To review the multifaceted roles of cysteinyl cathepsins in the pathogenesis and progression of cardiovascular diseases.
• To explore the complex, often opposing, functions of cathepsins in different cardiac conditions.
• To summarize the regulatory mechanisms influencing cathepsin activity during CVD development.

Main Methods:

• Literature review of studies on cysteinyl cathepsins and cardiovascular diseases.
• Analysis of cathepsin localization, regulation, and functional impact in various CVD models.
• Synthesis of information regarding cathepsin involvement in key cellular processes relevant to CVD.

Main Results:

• Cysteinyl cathepsins exhibit diverse roles in CVD, acting as pathogenic factors in aortic diseases (e.g., atherosclerosis) but showing cardioprotective effects in other conditions (e.g., hypertension, myocardial infarction).
• Cathepsin activity is modulated by inflammatory cytokines, growth factors, oxidative stress, and other stimuli during CVD.
• These proteases influence critical pathways including inflammation, immunity, cell migration, lipid metabolism, angiogenesis, cell death, signaling, and fibrosis.

Conclusions:

• Cysteinyl cathepsins are key players in cardiovascular pathophysiology, with context-dependent roles.
• Understanding cathepsin regulation and function is crucial for developing novel therapeutic strategies for CVD.
• This review honors Dr. Nobuhiko Katunuma's foundational contributions to cathepsin research.