Limits...
Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease

View Article: PubMed Central - PubMed

ABSTRACT

Aging and developmental programming are both associated with oxidative stress and endothelial dysfunction, suggesting common mechanistic origins. However, their interrelationship has been little explored. In a rodent model of programmed cardiovascular dysfunction we determined endothelial function and vascular telomere length in young (4 mo) and aged (15 mo) adult offspring of normoxic or hypoxic pregnancy with or without maternal antioxidant treatment. We show loss of endothelial function [maximal arterial relaxation to acetylcholine (71 ± 3 vs. 55 ± 3%) and increased vascular short telomere abundance (4.2–1.3 kb) 43.0 ± 1.5 vs. 55.1 ± 3.8%) in aged vs. young offspring of normoxic pregnancy (P < 0.05). Hypoxic pregnancy in young offspring accelerated endothelial dysfunction (maximal arterial relaxation to acetylcholine: 42 ± 1%, P < 0.05) but this was dissociated from increased vascular short telomere length abundance. Maternal allopurinol rescued maximal arterial relaxation to acetylcholine in aged offspring of normoxic or hypoxic pregnancy but not in young offspring of hypoxic pregnancy. Aged offspring of hypoxic allopurinol pregnancy compared with aged offspring of untreated hypoxic pregnancy had lower levels of short telomeres (vascular short telomere length abundance 35.1 ± 2.5 vs. 48.2 ± 2.6%) and of plasma proinflammatory chemokine (24.6 ± 2.8 vs. 36.8 ± 5.5 pg/ml, P < 0.05). These data provide evidence for divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease, and aging being decelerated by antioxidants even prior to birth.—Allison, B. J., Kaandorp, J. J., Kane, A. D., Camm, E. J., Lusby, C., Cross, C. M., Nevin-Dolan, R., Thakor, A. S., Derks, J. B., Tarry-Adkins, J. L., Ozanne, S. E., Giussani, D. A. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease.

No MeSH data available.


Related in: MedlinePlus

Effects of aging, developmental hypoxia and maternal allopurinol inflammatory markers. Values are means ± sem for the plasma concentration (pg/ml) of the proinflammatory chemokine KC/GRO in 4- and 15-mo-old offspring of untreated normoxic (white bars) or hypoxic (black bars) pregnancy (A) and in 4- and 15-mo-old offspring of normoxic (stippled bars) or hypoxic (dark gray bars) pregnancy treated with allopurinol (B). Bars with different letters are significantly (P < 0.05) different (2-way ANOVA and post hoc Tukey’s test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5036970&req=5

Figure 3: Effects of aging, developmental hypoxia and maternal allopurinol inflammatory markers. Values are means ± sem for the plasma concentration (pg/ml) of the proinflammatory chemokine KC/GRO in 4- and 15-mo-old offspring of untreated normoxic (white bars) or hypoxic (black bars) pregnancy (A) and in 4- and 15-mo-old offspring of normoxic (stippled bars) or hypoxic (dark gray bars) pregnancy treated with allopurinol (B). Bars with different letters are significantly (P < 0.05) different (2-way ANOVA and post hoc Tukey’s test).

Mentions: Plasma concentrations of the inflammatory markers IFN-γ, IL-5, and C-reactive protein were similar in offspring of normoxic or hypoxic pregnancy at 4 and 15 mo of age (Table 1). However, the plasma concentration of the proinflammatory chemokine KC/GRO, the rodent equivalent of human IL-8 (41), was significantly elevated in aged offspring of hypoxic pregnancy relative to aged offspring of normoxic pregnancy (Fig. 3). Furthermore, maternal treatment with allopurinol prevented the increase in plasma KC/GRO in aged offspring of hypoxic pregnancy (Fig. 3).


Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease
Effects of aging, developmental hypoxia and maternal allopurinol inflammatory markers. Values are means ± sem for the plasma concentration (pg/ml) of the proinflammatory chemokine KC/GRO in 4- and 15-mo-old offspring of untreated normoxic (white bars) or hypoxic (black bars) pregnancy (A) and in 4- and 15-mo-old offspring of normoxic (stippled bars) or hypoxic (dark gray bars) pregnancy treated with allopurinol (B). Bars with different letters are significantly (P < 0.05) different (2-way ANOVA and post hoc Tukey’s test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036970&req=5

Figure 3: Effects of aging, developmental hypoxia and maternal allopurinol inflammatory markers. Values are means ± sem for the plasma concentration (pg/ml) of the proinflammatory chemokine KC/GRO in 4- and 15-mo-old offspring of untreated normoxic (white bars) or hypoxic (black bars) pregnancy (A) and in 4- and 15-mo-old offspring of normoxic (stippled bars) or hypoxic (dark gray bars) pregnancy treated with allopurinol (B). Bars with different letters are significantly (P < 0.05) different (2-way ANOVA and post hoc Tukey’s test).
Mentions: Plasma concentrations of the inflammatory markers IFN-γ, IL-5, and C-reactive protein were similar in offspring of normoxic or hypoxic pregnancy at 4 and 15 mo of age (Table 1). However, the plasma concentration of the proinflammatory chemokine KC/GRO, the rodent equivalent of human IL-8 (41), was significantly elevated in aged offspring of hypoxic pregnancy relative to aged offspring of normoxic pregnancy (Fig. 3). Furthermore, maternal treatment with allopurinol prevented the increase in plasma KC/GRO in aged offspring of hypoxic pregnancy (Fig. 3).

View Article: PubMed Central - PubMed

ABSTRACT

Aging and developmental programming are both associated with oxidative stress and endothelial dysfunction, suggesting common mechanistic origins. However, their interrelationship has been little explored. In a rodent model of programmed cardiovascular dysfunction we determined endothelial function and vascular telomere length in young (4 mo) and aged (15 mo) adult offspring of normoxic or hypoxic pregnancy with or without maternal antioxidant treatment. We show loss of endothelial function [maximal arterial relaxation to acetylcholine (71 &plusmn; 3 vs. 55 &plusmn; 3%) and increased vascular short telomere abundance (4.2&ndash;1.3 kb) 43.0 &plusmn; 1.5 vs. 55.1 &plusmn; 3.8%) in aged vs. young offspring of normoxic pregnancy (P &lt; 0.05). Hypoxic pregnancy in young offspring accelerated endothelial dysfunction (maximal arterial relaxation to acetylcholine: 42 &plusmn; 1%, P &lt; 0.05) but this was dissociated from increased vascular short telomere length abundance. Maternal allopurinol rescued maximal arterial relaxation to acetylcholine in aged offspring of normoxic or hypoxic pregnancy but not in young offspring of hypoxic pregnancy. Aged offspring of hypoxic allopurinol pregnancy compared with aged offspring of untreated hypoxic pregnancy had lower levels of short telomeres (vascular short telomere length abundance 35.1 &plusmn; 2.5 vs. 48.2 &plusmn; 2.6%) and of plasma proinflammatory chemokine (24.6 &plusmn; 2.8 vs. 36.8 &plusmn; 5.5 pg/ml, P &lt; 0.05). These data provide evidence for divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease, and aging being decelerated by antioxidants even prior to birth.&mdash;Allison, B. J., Kaandorp, J. J., Kane, A. D., Camm, E. J., Lusby, C., Cross, C. M., Nevin-Dolan, R., Thakor, A. S., Derks, J. B., Tarry-Adkins, J. L., Ozanne, S. E., Giussani, D. A. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease.

No MeSH data available.


Related in: MedlinePlus