# Role of vascular smooth muscle Bcl11b in arterial stiffness

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $165,000

## Abstract

Nicotinamide adenine dinucleotide (NAD+) is an essential co-factor for the activity of enzymes involved
in cellular metabolic homeostasis, redox balance, DNA synthesis, and stress response. NAD+ is
synthetized de novo from tryptophan, but its function is so fundamental to cellular function that mammals
evolved a salvage pathway to continuously replenish intracellular NAD+ using a variety of substrates.
Among NAD+ precursors, nicotinamide (NAM), nicotinamide mononucleotide (NMN), and nicotinamide
riboside (NR) are commercially available as dietary supplements; however, we do not fully understand
the full spectrum of their biological effects, specifically on the cardiovascular system, which will be the
focus of this research proposal. Of clinical importance, NAD+ levels have been shown to drastically
decrease with obesity and aging, which are the highest risk factors for cardiovascular disease (CVD).
We postulate that replenishing intracellular NAD+ via dietary supplements is a viable approach to
attenuating CVD, which remain the primary cause of morbidity and mortality in an increasingly obese
and aging American population. Recent evidence indicate that administering NAM and NMN to
experimental animals significantly increases NAD+ levels in heart and fat, preventing diabetes and
diabetic heart failure in obese mice/rats. Moreover, NMN has been shown to prevent arterial stiffening
and hypertension in aged mice. However, whether dietary supplementation of NMN or NR increases
NAD+ levels in the vasculature and whether these increased levels lead to molecular mechanisms with
potentially beneficial vascular effects are not fully understood. The goal of this supplemental proposal
is to investigate whether dietary supplementation of NMN, NR, or a combination of the two supplements
to mice increases NAD+ levels in the vasculature (Aim 1). We will also determine whether this
supplementation can preserve vascular function, measured as arterial compliance and blood pressure,
in obese and aged mice, by increasing NAD+ levels in vascular cells and activating downstream anti-
inflammatory and anti-oxidant pathways (Aim 2). Successful completion of these preclinical, proof-of-
concept studies will fill a gap in knowledge on the vascular effects of NAD+ precursors and will guide
rational use of NAD+ precursors (NMN, NR) as dietary supplements.

## Key facts

- **NIH application ID:** 10393739
- **Project number:** 3R01HL136311-04S1
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Francesca Seta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $165,000
- **Award type:** 3
- **Project period:** 2021-07-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10393739

## Citation

> US National Institutes of Health, RePORTER application 10393739, Role of vascular smooth muscle Bcl11b in arterial stiffness (3R01HL136311-04S1). Retrieved via AI Analytics 2026-09-03 from https://api.ai-analytics.org/grant/nih/10393739. Licensed CC0.

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