Megakaryocyte Ploidy and Platelet Changes in Human Diabetes and Atherosclerosis

Abstract

Altered platelet morphology and function have been reported in patients with diabetes. They are likely to be associated with the pathological processes and increased risk of vascular disease seen in these patients. Mean platelet volume (MPV), platelet count, and megakaryocyte (MK) ploidy (DNA content) were measured in (1) nondiabetics with normal coronary arteries, (2) nondiabetics with coronary artery atherosclerosis, (3) diabetics without evidence of vascular complications, and (4) diabetics with vascular disease. The platelet count (+/- SD) was increased in all groups but only significantly in the diabetics with vascular disease (236 +/- 65 versus 250 +/- 54 versus 257 +/- 64 versus 295 +/- 90 [P < or = .05] x 10(9)/L, for groups, I, II, II, and IV, respectively). The MPV was significantly increased in patients with atherosclerosis (7.0 +/- 0.4 versus 8.0 +/- 1.2 [P < or = .05] versus 7.2 +/- 0.9 versus 8.1 +/- 0.9 [P < or = .05] IL). Geometric mean MK ploidy was significantly increased in all groups compared with controls (16 +/- 1.5 versus 18.7 +/- 1.8 [P < or = .05] versus 19.8 +/- 1.6 [P < or = .05] versus 20.1 +/- 2.7 [P < or = .05]). Furthermore, some patients with vascular disease and/or diabetes had a modal ploidy shift from 16 (the normal mammalian modal ploidy) to 32, with a concomitant reduction of MKs in the 8 and 16 ploidy classes. This shift was seen particularly in the diabetics with vascular disease (P = .007). Interleukin-6 (IL-6) levels were measured and were elevated in patients with atherosclerosis; the highest levels were found in the diabetic patients (0.7 +/- 0.9 versus 5.3 +/- 5.5 [P < or = .05] versus 2.5 +/- 2.8 versus 6.7 +/- 5.5 [P < or = .05] ng/L). In the diabetic patients with atherosclerosis, fibrinogen levels were also increased (2.85 +/- 0.76 versus 3.34 +/- 1.32 versus 2.43 +/- 1.50 versus 5.59 +/- 1.72 [P< or = .05] g/L). Furthermore, IL-6 levels correlated with MK ploidy (r = .45, P = .009) and fibrinogen levels (r = .5, P = .0001). This study demonstrates that patients with vascular disease, particularly diabetics, have an altered MK ploidy distribution, showing a shift toward higher ploidy in association with an increased platelet mass (count x volume). Changes in platelets in diabetes probably reflect MK changes, which themselves are a response to systemic change.

Association between mean platelet volume and hypertension incidence

“…25 Cytokines such as interleukin-6 are a possible regulator of the increases in MPV caused by megakaryocyte ploidy. 26 Inflammatory markers such as C-reactive protein and interleukin-6 have been reported to be independently predictive of hypertension. 27,28 (n = 2257) P P for …”

Effect of agmatine on the blood system parameters of rats under the condition of experimental diabetes mellitus

“…Посилення цих процесів супроводжу-ється секрецією вмісту тромбоцитарних гранул, зокрема, ростових факторів, які викликають активацію мегакаріоцитарно-тромбоцитарної системи -стимулюється утворення мегакаріоцитів, збільшується їхня плоїдність, розмір і швидкість дозрі-вання [17]. Наслідком цього є підвищення продукції тромбоцитів [10], причому за умов ЦД вони мають більший розмір порівняно із нормою та є більш реактивними [16]. Результатом усіх цих змін є посилення гемокоагуляції та розвиток судинної дисфункції, що відіграє ключову роль у розвитку діабетичних ангіопатій [3].…”

Genetic variation of the platelet- surface integrin GPIIb-IIIa ( PIA1/A2- SNP) shows a high association with Type 2 diabetes mellitus

“…The nucleated bone marrow megakaryocytes have been shown to be altered both in terms of DNA content (ploidy) and quantitative GPIIb-IIIa expression in the diabetic BB-rat model and in human Type 2 diabetes patients [8,9].…”