Characterization of a resident population of adventitial macrophage progenitor cells in postnatal vasculature.

Rationale: Macrophages regulate blood vessel structure and function in health and disease. The origins of tissue macrophages are diverse, with evidence for local production and circulatory renewal.

Objective: We identified a vascular adventitial population containing macrophage progenitor cells and investigated their origins and fate.

Tissue factor pathway inhibitor blocks angiogenesis via its carboxyl terminus.

Objective: Tissue factor pathway inhibitor (TFPI) is the primary regulator of the tissue factor (TF) coagulation pathway. As such, TFPI may regulate the proangiogenic effects of TF. TFPI may also affect angiogenesis independently of TF, through sequences within its polybasic carboxyl terminus (TFPI C terminus [TFPIct]).

Identification of a monocyte-predisposed hierarchy of hematopoietic progenitor cells in the adventitia of postnatal murine aorta.

Background: Hematopoiesis originates from the dorsal aorta during embryogenesis. Although adult blood vessels harbor progenitor populations for endothelial and smooth muscle cells, it is not known if they contain hematopoietic progenitor or stem cells. Here, we hypothesized that the arterial wall is a source of hematopoietic progenitor and stem cells in postnatal life.

Vascular-directed tissue factor pathway inhibitor overexpression regulates plasma cholesterol and reduces atherosclerotic plaque development.

Rationale: Tissue factor pathway inhibitor (TFPI) is a potent regulator of the tissue factor pathway and is found in plasma in association with lipoproteins.

Objective: To determine the role of TFPI in the development of atherosclerosis, we bred mice which overexpress TFPI into the apolipoprotein E-deficient (apoE(-/-)) background.

Methods And Results: On a high-fat diet, smooth muscle 22alpha (SM22alpha)-TFPI/apoE(-/-) mice were shown to have less aortic plaque burden compared to apoE(-/-) mice.

Tissue factor pathway inhibitor overexpression inhibits hypoxia-induced pulmonary hypertension.

Pulmonary hypertension (PH) is a commonly recognized complication of chronic respiratory disease. Enhanced vasoconstriction, pulmonary vascular remodeling, and in situ thrombosis contribute to the increased pulmonary vascular resistance observed in PH associated with hypoxic lung disease. The tissue factor pathway regulates fibrin deposition in response to acute and chronic vascular injury.