CD59 or C3 are not requred for angiotensin II-dependent hypertension or hypertrophy in mice

Area of Science:

• Immunology
• Cardiovascular Physiology
• Innate Immunity

Background:

• The complement system is a key pro-inflammatory innate immune pathway.
• Serum complement activity correlates with systolic blood pressure in humans.
• The role of individual complement components in hypertension and cardiac hypertrophy in vivo remains unexamined.

Purpose of the Study:

• To investigate the in vivo role of CD59a and C3 in regulating vascular function, hypertension, and cardiac hypertrophy.
• To characterize responses to angiotensin II in mice deficient in CD59a or C3.

Main Methods:

• Utilized knockout mouse models deficient in CD59a or C3.
• Administered angiotensin II and noradrenaline infusions to induce hypertension and hypertrophy.
• Assessed systolic blood pressure, vascular function (acetylcholine and sodium nitroprusside-dependent dilatation), and cardiac hypertrophy.
• Measured platelet endothelial cell adhesion molecule-1 (PECAM-1) expression, membrane attack complex deposition, plasma nitrate/nitrite, and aortic cyclic guanosine monophosphate levels.

Main Results:

• CD59a(-/-) mice exhibited slightly elevated systolic blood pressure and reduced PECAM-1 expression with increased membrane attack complex deposition.
• Vascular function, plasma nitrate/nitrite, and aortic cyclic guanosine monophosphate levels were unchanged in CD59a(-/-) mice.
• Both CD59a(-/-) and C3(-/-) mice showed similar hypertension and cardiac hypertrophy responses to angiotensin II compared to wild-type mice.

Conclusions:

• CD59a deficiency is linked to vascular alterations potentially indicating early complement-mediated damage.
• CD59a and C3 do not play a direct role in the development of angiotensin II-dependent hypertension or cardiac hypertrophy in vivo.
• Caution is advised regarding complement intervention strategies for hypertension and heart failure.