Molecular Targets of Reactive Oxygen Species in Vascular Cells

ROS play an important role in normal cellular signaling and function.84-86 Redox-sensitive signaling molecules that have been implicated in cardiovascular disease include transcription factors, protein tyrosine phosphatases, protein

Î Vascular Tone

Inflammation

  • VSMC proliferation
  • VSMC hypertrophy

T ECM proteins

Î Vascular Tone

Inflammation

  • VSMC proliferation
  • VSMC hypertrophy

T ECM proteins

Vascular Remodeling

Fig. 4.3 Redox-dependent signaling pathways in vascular cells. Intracellular ROS modify the activity of tyrosine kinases, such as Src, Ras, JAK2, Pyk2, P13K and EGFR, as well as MAP kinases, particularly p38MAP kinase, JNK and ERK5. ROS may inhibit PTP activity, further contributing to PTK activation. ROS also influence gene and protein expression by activating transcription factors, such as NFkB and AP-1. ROS stimulate ion channels, such as plasma membrane Ca2+ and K+ channels, leading to changes in cation concentration. Activation of these redox-sensitive pathways results in numerous cellular responses, which is uncontrolled, could contribute to altered vascular tone, increased vascular smooth muscle cell (VSMC) growth, inflammation and increased deposition of extracellular matrix protein (EMP), leading to vascular remodeling in hypertension. -, inhibitory effect; +, stimulatory effect tyrosine kinases, mitogen-activated protein (MAP) kinases, and ion channels (Fig. 4.3). Of these, transcription factors and protein tyrosine phosphatases appear to be directly regulated by ROS,87-89 whereas the other signaling molecules are probably influenced by ROS through indirect mechanisms.

Your Heart and Nutrition

Your Heart and Nutrition

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