That portion will generally not count. E-2 requires the investor's funds to be at risk, and a loan secured by the enterprise's own assets places the risk on the business, not the investor. Money borrowed on the couple's personal liability against their own property does count.
The security decides whether the loan is your risk or the bank's
The consular guidance distinguishes between indebtedness secured by the assets of the enterprise, which is not an investment because the investor is not personally at risk, and loans secured by the investor's personal assets or unsecured loans on the investor's personal signature, which are. For a Kent couple buying a U.S. nursery, a line of credit against their Canadian home is their own capital in the required sense, while a loan the bank secures against the greenhouses, delivery vehicles and plant stock is not. If the enterprise-secured loan covers most of the price, the investment presented will be far smaller than the purchase price, and the substantiality assessment is made on the smaller figure. The remaining conditions—treaty nationality of both investors and of at least half the ownership, a real operating business that is not marginal, and the couple's control—must each be shown regardless of how the money is raised.
Hypothetical example: a Canadian citizen acquires a small commercial laundry using a loan secured only by her personal brokerage account. The first review follows the loan proceeds, collateral and closing documents to determine whether her own assets remain exposed if the business fails. That differs from a loan secured solely by the acquired enterprise. The signed security agreement, not the lender's marketing description, settles the point, and the enterprise still must be real, operating and more than marginal.