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

Abstract

Summary Complement is a major pro‐inflammatory innate immune system whose serum activity correlates with systolic blood pressure in humans. To date, no studies using in vivo models have directly examined the role of individual complement components in regulating vessel function, hypertension and cardiac hypertrophy. Herein, in vivo responses to angiotensin (ang) II were characterized in mice deficient in CD59a or C3. CD59a–/– mice had slightly but significantly elevated systolic blood pressure (107·2 ± 1·7 mmHg versus 113·8 ± 1·31 mmHg, P < 0·01, for wild‐type and CD59a–/–, respectively). Aortic rings from CD59a–/– mice showed significantly less platelet endothelial cell adhesion molecule‐1 (PECAM‐1) expression, with elevated deposition of membrane attack complex. However, acetylcholine‐ and sodium nitroprusside‐dependent dilatation, plasma nitrate/nitrite and aortic cyclic guanosine monophosphate levels were unchanged from wild‐type. Also, in vivo infusion with either ang II or noradrenaline caused similar hypertension and vascular hypertrophy to wild‐type. Mice deficient in C3 had similar basal blood pressure to wild type and showed no differences in hypertension or hypertrophy responses to in vivo infusion with ang II. These data indicate that CD59a deficiency is associated with some vascular alterations that may represent early damage occurring as a result of increased complement attack. However, a direct role for CD59a or C3 in modulating development of ang II‐dependent hypertension or hypertrophy in vivo is excluded and we suggest caution in development of complement intervention strategies for hypertension and heart failure.

Circulating neutrophils maintain physiological blood pressure by suppressing bacteria and IFNγ-dependent iNOS expression in the vasculature of healthy mice

“…Systolic blood pressure and neutrophil counts following RB6-8C5 administration were unchanged from control C3 −/− mice, who have normal basal blood pressure ( Figure 3 D). 24 This implicates C3b opsonization of neutrophils in their RB6-8C5–mediated clearance.…”

Heme oxygenase-1 expression is down-regulated by angiotensin II and under hypertension in human neutrophils

“…The first is the important role of oxidative stress and inflammation in the pathogenesis of vascular disease and hypertension [31], which may be mediated or promoted by circulating blood cells [32]. The second is that up-regulation of HO-1 expression is currently well-accepted as a protective mechanism against intracellular oxidative stress [33].…”

Urinary alpha-1 antitrypsin and CD59 glycoprotein predict albuminuria development in hypertensive patients under chronic renin-angiotensin system suppression

“…However this increment did not occur in other renal diseases particularly those with tubulo-interstitial damage and a similar situation could happen in our patients [ 36 ]. Interestingly, a slight increase in blood pressure was observed in CD59 knockout mice [ 38 ]. In agreement, a reduced expression of CD59 in endothelial cells from hypertensive patients has been described, suggesting a potential role in development of hypertension and increased CV risk [ 39 ].…”