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The chemokine CXCL4/platelet factor 4 (PF4) gene, a key player in myelofibrosis, was knocked out by CRISPR/Cas9 in induced pluripotent stem cells (iPS cells) of a polycythemia vera (PV) patient with JAK2 V617F mutation. Two CXCL4 KO iPS cell lines with and without JAK2 V617F mutation (UKAi002-B-1 and UKAi002-A-1, respectively) were generated. CXCL4 KO iPS cells showed deletion of exon 1 and complete loss of CXCL4 protein. Pluripotency of iPS cells was confirmed by expression of pluripotency markers and trilineage differentiation. CXCL4 KO iPS cells are expected to provide a valuable tool for investigating the role of CXCL4 in human diseases., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

To determine the role of the sympathetic nervous system in myocardial ischemia with essential hypertension, plasma norepinephrine, heart rate (HR), blood pressure (BP), and the HR.BP double product at the time of silent ischemia during pacing and exercise treadmill test (ETT) were compared with basal values in 20 patients with sustained essential hypertension and stable angina, 3 to 60 days (12.6 +/- 11.6) after discontinuation of all antihypertensive and coronary vasodilator therapy. Group I (N = 6) had silent ischemia with a higher HR.BP product at ETT than at pacing (ratio = 157 +/- 10.4% [+/- SD] v a value in group II [N = 5] of 102 +/- 18.8 [P less than .01]. Group III (N = 9) had no silent ischemia at ETT or pacing. Group I v group II plasma norepinephrine levels at rest and with pacing silent ischemia were 76 +/- 37 v 138 +/- 36 pg/mL, P less than .02, and 101 +/- 50 v 230 +/- 43 pg/mL, P less than .01, respectively. In groups I and II plasma norepinephrine levels were significantly lower than those of group III. Eleven of 20 patients had ischemia on pacing or ETT. Left ventricular myocardial mass were greater (224 +/- 49 v 180 +/- 28 g, p less than .05), HR (67 +/- 13 v 76 +/- 11 beats/min, P = NS) and plasma norepinephrine levels at rest (104 +/- 47 v 241 +/- 99 pg/mL, P less than .01), pacing (160 +/- 81 v 338 +/- 94 pg/mL, P less than .01), and ETT (758 +/- 268 v 1203 +/- 611 pg/mL, P less than .05), were lower in patients with ischemia (N = 11, group II) than in patients without ischemia (N = 9, group III) on pacing or ETT. Eight patients were on reserpine prestudy; reserpine prestudy was associated with lower basal HR (63 +/- 9 v 76 +/- 12 beats/min, P less than .05) and plasma norepinephrine (106 +/- 48 v 169 +/- pg/mL, P less than .07) and greater ratio of HR.BP double product on ETT/pacing, (141 +/- 33 v 111 +/- 19, P less than .02). The sympathetic nervous tone of group I was low at baseline but there may have been raised alpha/beta-receptor responsiveness to laboratory stresses with concomitant micro/macrovascular constriction at higher oxygen demand.(ABSTRACT TRUNCATED AT 400 WORDS)

We examine the heart's involvement in arterial hypertension, reporting on several studies of hypertensive patients showing that left ventricular myocardial mass is a significant prognostic indicator of essential hypertension and that left ventricular hypertrophy (LVH) correlates with an induced increase in Ca2+ concentration in platelets. We also consider the LVH variant of asymmetric hypertrophy and the role of the hypertensive heart in coronary insufficiency, and we speculate on the significance of the degree of LVH and asymmetric hypertrophy as risk factors for predicting cardiac complications of essential hypertension.