The invention encompasses compositions and methods for effectively interfering, reducing and preventing conversion of
vascular smooth muscle cells (VSMCs) and circulating stem cells to osteoblastic bone-like cells, thereby reducing and / or preventing
vascular calcification (VC) or
calcium mineral (hydroxyapatite) deposition in the vasculature. The severity and extent of
calcification in the major arteries reflect atherosclerotic plaque burden and strongly predict cardiovascular morbidity and mortality. The present inventive compositions used for administration to human and other mammalian subjects comprise select actives that inhibit, interfere or regulate the biochemical processes leading to such
calcification and include (1) at least one agent that modulates expression and / or activity of
peroxisome activated
protein receptor gamma (PPAR-γ); (2) at least one agent that inhibits expression and / or suppresses activity of one or more of the osteogenic transcription factors (Cbfα1 / Runx2, Osterix, Msx2) and β-
catenin signaling; (3) at least one agent that inhibits expression and / or suppresses activity of one or more of bone morphogenetic proteins (BMPs: BMP 2 and 4),
alkaline phosphatase (ALP), and
osteocalcin; (4) at least one agent that inhibits the activity of
Reactive Oxygen Species (ROS); and (5) at least one agent that suppresses one or more of inflammatory mediators including interleukins IL-1α, IL-1β, IL-6, NF-κB, TNF-α, matrix metalloproteinases (MMPs) and
prostaglandin E2 (PGE2). The compositions may further comprise at least one agent that promotes expression and / or
carboxylation of matrix Gla
protein (MGP). Advantageously, these select actives include materials such as phytonutrients, vitamins and minerals that have been broadly used in food and drink products and are safe for human and pet / animal consumption. Compositions with such combinations have the ability to prevent, treat and reverse VC not only in
coronary arteries but also in other tissues capable of undergoing undesirable
calcification. In addition the present compositions are effective against associated conditions or contributory factors / inducers to VC, including diabetes,
obesity, hypertension,
inflammation,
oxidative stress,
osteoporosis and
arthritis.