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. Author manuscript; available in PMC: 2025 Jul 1.
Published in final edited form as: Physiol Rev. 2025 Feb 18;105(3):1075–1171. doi: 10.1152/physrev.00028.2024

Figure 21. Distinct and shared cellular and molecular mechanisms involved in neurovascular coupling defects in sporadic and genetic cSVDs.

Figure 21.

During aging (B), there is an increased arterial stiffness and a reduction in arterial SMC coverage crippling arterial dilation. In angiotensin II-dependent hypertension, one mechanism (C) involves an increased production of reactive oxygen species (ROS) by perivascular macrophages (PVM) that reduces the bioavailability of nitric oxide (NO) leading to a reduction in vasodilation. In CADASIL (D), TIMP3 accumulation in the pericyte-endothelial cell basement membranes causes a decrease in ATP-dependent synthesis of PIP2 leading to a reduction in Kir2.1 activity and crippling the endothelial cell (EC) retrograde hyperpolarization. In the COL4A1/2 cSVD (E), NVC is also caused by a reduction in Kir2.1 activity but this arises from a reduced PIP2 availability as a consequence of abnormal basement membranes (dashed grey line below SMCs).