Angiotensinogen Expression in Human Adipose Tissue (page 41)
Blood pressure is a heritable trait; the genetic causes of essential hypertension remain unclear. Despite being the first gene linked to hypertension, the importance of polymorphisms in angiotensinogen, the precursor to angiotensin-II, remains controversial. The renin–angiotensin system has both endocrine and intracrine functions controlling arterial pressure. The mechanisms regulating angiotensinogen expression is complicated. Because sequence variants in the promoter may differentially affect transcription factor binding, the mechanisms regulating angiotensinogen may differ depending on the polymorphism(s) carried. The current issue of Hypertension reports an effective strategy to examine whether variation in the angiotensinogen promoter effects its expression through differential binding of transcription factors in adipose tissue. The investigators report increased expression of angiotensinogen mRNA and binding of the transcription factor USF2 in chromatin specifically from the −20C allele in subcutaneous adipose tissue from subjects heterozygous for the −20A/C alleles of angiotensinogen. Thus, subjects carrying high-expressing alleles may have increased levels of angiotensinogen and angiotensin-II in some fat depots. This may be clinically important because circulating angiotensinogen derived from adipose tissue is increased in obesity and evidence implicates a role for angiotensin-II derived from adipose angiotensinogen in the regulation of metabolism and blood pressure. Consequently, further studies will need to assess whether this and other polymorphisms control the level of angiotensin-II in hypertensive and obese subjects.
CD8+ T Cells and Chemokines in Human Hypertension (page 126)
The pathogenic role of T cells in the development of hypertension has been well documented in animal studies. However, the existence of T-cell–driven inflammation in human hypertension has not been demonstrated. In this issue of Hypertension, Youn et al reported an increased fraction of immunosenescent, proinflammatory, cytotoxic CD8+ T cell, and increased circulating levels of T cell chemokines (MIG, IP-10, and I-TAC) in patients with hypertension. In patients with hypertensive nephrosclerosis, I-TAC was expressed more abundantly in the proximal and distal tubules. This evidence, along with an increased level of serum granzyme B, supports the increased activity of cytotoxic T cells in human hypertension. The authors provide evidence for the first time in favor of the existence of T-cell–driven inflammation in human hypertension.
Cardiac Effects of Hyperaldosteronism (page 62)
Affecting >11% of the patients referred to specialized hypertension centers, primary aldosteronism (PA) is the most common endocrine cause of high blood pressure. Furthermore, it induces cardiovascular damage in excess of that expected based on the degree of blood pressure elevation. PA is potentially curable with a targeted treatment, but whether normalization of the blood pressure and regression of associated cardiovascular damage could be achieved in the long term remained uncertain. Rossi et al prospectively assigned 180 PA patients to either adrenalectomy (n=110) or medical therapy (n=70), based on whether there was lateralization of aldosterone excess at adrenal vein sampling. Long-term follow-up study with serial echocardiography evaluations showed for the first time in a prospective study that atrial fibrillation was ≈6-fold higher in PA than in essential hypertensive patients. After treatment blood pressure fell comparably in adrenalectomized and medically treated PA, as it did in optimally treated essential hypertensives. Left ventricular (LV) mass index and the rate of LV hypertrophy also fell mainly through LV inward remodeling in PA patients. Notwithstanding this, the rate of LV mass that was disproportionally elevated for cardiac workload and sex in PA subjects unexpectedly increased. While highlighting the cardiovascular consequences of PA patients, these findings underscore the importance of a timely identification of PA to enable reversal of the LV abnormalities and lowering cardiovascular risk.
- © 2013 American Heart Association, Inc.